{{Short description|Species of virus}} {{AI-generated|date=December 2025}} {{Redirect|FIV}} {{distinguish|text=FIP, another feline disease caused by a virus that attacks the immune system}} {{Virusbox | name = Feline immunodeficiency virus | image = PDB 4fiv EBI.jpg | image_alt = | image_caption = | parent = Lentivirus | species = Lentivirus felimdef | synonyms = | synonyms_ref = }}
'''Feline immunodeficiency virus''' ('''FIV''') is a lentivirus that affects cats worldwide with 2.5% to 4.4%<ref>{{Citation|author1=Valéria Maria Lara |author2=Sueli Akemi Taniwaki |author3=João Pessoa Araújo Júnior |year=2008|title=Occurrence of feline immunodeficiency virus infection in cats|journal=Ciência Rural|volume=38|issue=8|doi=10.1590/S0103-84782008000800024|postscript=.|page=2245|doi-access=free|hdl=11449/18125|hdl-access=free}}</ref><ref>{{Citation| doi = 10.1016/j.biologicals.2005.08.004| title = Feline immunodeficiency virus vaccine: Implications for diagnostic testing and disease management| year = 2005| author = Richards, J| journal = Biologicals| volume = 33| pages = 215–7| pmid = 16257536| issue = 4| postscript = . }}</ref> of felines being infected.
FIV was first isolated in 1986, by Niels C. Pedersen and Janet K. Yamamoto at the UC Davis School of Veterinary Medicine in a colony of cats that had a high prevalence of opportunistic infections and degenerative conditions, and was originally called ''feline T-lymphotropic virus''.<ref>{{Citation|title=Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome|journal=Science|year=1987|volume=235|pages=790–793| doi = 10.1126/science.3643650|author2=Ho EW|author3=Brown ML|display-authors=3|author=Pedersen NC|last4=Yamamoto|first4=J.|issue=4790|pmid=3643650|postscript=. |bibcode=1987Sci...235..790P}}</ref> It has since been identified in domestic cats.<ref name="Zislin, A 2005 219">{{Citation| doi = 10.1016/j.biologicals.2005.08.012| title = Feline immunodeficiency virus vaccine: A rational paradigm for clinical decision-making| year = 2005| author = Zislin, A| journal = Biologicals| volume = 33| pages = 219–20| pmid = 16257537| issue = 4| postscript = .}}</ref>
==Effects== {{Missing information|section|the disease effects that is '''''well sourced''''' (previous unsourced material was removed)|date=April 2026}} FIV is known in other feline species, and in fact is endemic in some large wildcats, such as African lions. Three main clades of FIV are recognized as of 2006: FIV-Ple (lion), FIV-Fca (domestic cat), and FIV-Pco (puma).<ref>{{cite journal |last1=Troyer |first1=JL |last2=Roelke |first2=ME |last3=Jespersen |first3=JM |last4=Baggett |first4=N |last5=Buckley-Beason |first5=V |last6=MacNulty |first6=D |last7=Craft |first7=M |last8=Packer |first8=C |last9=Pecon-Slattery |first9=J |last10=O'Brien |first10=SJ |title=FIV diversity: FIV Ple subtype composition may influence disease outcome in African lions. |journal=Veterinary Immunology and Immunopathology |date=15 October 2011 |volume=143 |issue=3–4 |pages=338–46 |doi=10.1016/j.vetimm.2011.06.013 |pmid=21723622 |pmc=3168974}}</ref> The host boundaries are usually well kept because of the limited types of APOBEC3 enzymes that viral infectivity factor can neutralize.<ref>{{cite journal |last1=Konno |first1=Y |last2=Nagaoka |first2=S |last3=Kimura |first3=I |last4=Yamamoto |first4=K |last5=Kagawa |first5=Y |last6=Kumata |first6=R |last7=Aso |first7=H |last8=Ueda |first8=MT |last9=Nakagawa |first9=S |last10=Kobayashi |first10=T |last11=Koyanagi |first11=Y |last12=Sato |first12=K |title=New World feline APOBEC3 potently controls inter-genus lentiviral transmission. |journal=Retrovirology |date=10 April 2018 |volume=15 |issue=1 |page=31 |doi=10.1186/s12977-018-0414-5 |pmid=29636069|pmc=5894237 |doi-access=free }}</ref>
{{Globalize|section|USA|2name=the United States|date=January 2019}}
===In the United States=== Consensus in the United States on whether there is a need to euthanize FIV-infected cats has not been established. The American Association of Feline Practitioners,<ref name="Nehring2024">{{cite journal |last1=Nehring |first1=M. |last2=Dickmann |first2=E. M. |last3=Billington |first3=K. |last4=VandeWoude |first4=S. |title=Study of feline immunodeficiency virus prevalence and expert opinions on standards of care |journal=Journal of Feline Medicine and Surgery |volume=26 |issue=7 |date=July 2024 |doi=10.1177/1098612X241245046 |pmid=39073897 |pmc=11292943}}</ref> as well as many feral cat organizations, recommends against euthanizing FIV-positive cats, or even spending funds to test for the virus.<ref>{{cite journal |last1=Little |first1=Susan |last2=Levy |first2=Julie |last3=Hartmann |first3=Katrin |last4=Hofmann-Lehmann |first4=Regina |last5=Hosie |first5=Margaret |last6=Olah |first6=Glenn |last7=Denis |first7=Kelly St |title=2020 AAFP Feline Retrovirus Testing and Management Guidelines |journal=Journal of Feline Medicine and Surgery |date=9 January 2020 |volume=22 |issue=1 |pages=5–30 |doi=10.1177/1098612X19895940 |doi-access=free |pmid=31916872|pmc=11135720 }}</ref>
==Pathology==
The virus gains entry to host cells through the interaction of its own envelope glycoproteins with the target cells' surface receptors. First, the SU glycoprotein binds to CD134, a receptor on the host cell. This initial binding changes the shape of the SU protein to one that facilitates interaction between SU and the chemokine receptor CXCR4.<ref>{{cite journal|last1=Hu|first1=Quiong-Ying|title=Mapping of Receptor Binding Interactions with the Fiv Surface Glycoprotein (SU); Implications Regarding Immune survelliance and cellular Targets of Infection|journal=Retrovirology: Research and Treatment|date=2012|volume=1|issue=11|pages=1–11|doi=10.4137/RRT.S9429|pmc=3523734|url=|pmid=23255871}}</ref> This interaction causes the viral and cellular membranes to fuse, allowing the transfer of the viral RNA into the cytoplasm, where it is reverse transcribed and integrated into the cellular genome through nonhomologous recombination. Once integrated into the host cell's genome, the virus can lie dormant in the asymptomatic stage for extended periods of time without being detected by the immune system or can cause lysis of the cell.<ref name="Lecollinet 2007 167–190"/><ref name="Hartmann 2011 190–201">{{Citation|last=Hartmann|first=Katrin|title=Clinical aspects of feline immunodeficiency and feline leukemia virus infection|journal=Veterinary Immunology and Immunopathy|year=2011|volume=143|issue=3–4|pages=190–201|doi=10.1016/j.vetimm.2011.06.003|pmid=21807418|pmc=7132395}}</ref>
CD134 is predominantly found on activated T cells and binds to OX40 ligand, causing T-cell stimulation, proliferation, activation, and apoptosis (3). This leads to a significant drop in cells that have critical roles in the immune system. Low levels of CD4+ and other affected immune-system cells cause the cat to be susceptible to opportunistic diseases once the disease progresses to ''feline acquired immune deficiency syndrome'' (FAIDS).<ref name="Yamamoto 2010 14–25=15 November 2011">{{Citation|last=Yamamoto|first=Janet|author2=Missa Sanou|author3= Jeffrey Abbott|author4= James Coleman|title=Feline immunodeficiency virus model for designing HIV/AIDS vaccines|journal=Current HIV Research|year=2010|volume=8|issue=1|pages=14–25|doi=10.2174/157016210790416361|pmid=20210778|pmc=3721975}}</ref>
==Transmission== The primary mode of transmission is via deep bite wounds, in which the infected cat's saliva enters the other cat's tissues. FIV may also be transmitted from pregnant females to their offspring in utero; however, this vertical transmission is considered to be relatively rare, based on the small number of FIV-infected kittens and adolescents.<ref name="cornellfiv">{{Citation|work=Cornell Feline Health Center|title=Feline Immunodeficiency Virus|publisher=Cornell University, College of Veterinary Medicine|author=American Association of Feline Practitioners|year=2002|access-date=2008-11-12|url=https://www.vet.cornell.edu/fhc/brochures/fiv.html}}</ref><ref name="Yamamoto 2010 14–25=15 November 2011"/> This differs from feline leukemia virus (FeLV), which may be spread by more-casual, nonaggressive contact, such as mutual grooming and sharing of food bowls.{{citation needed|date=September 2019}}
Risk factors for infection include male sex, adulthood, and outdoor access. One case study conducted in São Paulo found that 75% of FIV-infected cats were males. Higher rates of infection in males than females occur because males defending their territory bite more frequently.<ref name="Hartmann 2011 190–201"/>
==Disease stages== FIV progresses through similar stages to HIV. The initial stage, or acute phase, is accompanied by mild symptoms such as lethargy, anorexia, fever, and lymphadenopathy (swelling of the lymph nodes).<ref name="Yamamoto 2010 14–25=15 November 2011"/> This initial stage is fairly short and is followed by the asymptomatic stage. Here the cat demonstrates no noticeable symptoms for a variable length of time. Some cats stay in this latent stage for only a few months, but for some it can last for years. Factors that influence the length of the asymptomatic stage include the pathogenicity of the infecting virus and FIV subtype (A–E), the age of the cat, and exposure to other pathogens. Finally, the cat progresses into the final stage (known as the feline acquired immune deficiency syndrome (FAIDS) stage), wherein the cat is extremely susceptible to secondary diseases that inevitably are the cause of death.<ref name="Hartmann 2011 190–201"/>
==Testing== Veterinarians will check a cat's history, look for clinical signs, and possibly administer a blood test for FIV antibodies. FIV affects 2–3% of cats in the US and testing is readily available. This testing identifies those cats that carry the FIV antibody but does not detect the actual virus.<ref>{{cite journal |last1=Little |first1=S. |last2=Levy |first2=J. |last3=Hartmann |first3=K. |last4=Hofmann-Lehmann |first4=R. |last5=Hosie |first5=M. |last6=Olah |first6=G. |last7=Denis |first7=K. S. |title=2020 AAFP Feline Retrovirus Testing and Management Guidelines |journal=Journal of Feline Medicine and Surgery |volume=22 |issue=1 |pages=5–30 |date=January 2020 |doi=10.1177/1098612X19895940 |pmid=31916872 |pmc=11135720}}</ref>
"False positives" may occur when the cat carries the antibody (which is harmless) but does not carry the virus. The most frequent occurrence of this is when kittens are tested after ingesting the antibodies from mother's milk (passive immunity), and when testing cats that have been previously vaccinated for FIV (active immunity). For this reason, neither kittens under eight weeks nor cats that have been previously vaccinated are tested. Kittens and young cats that test positive for the FIV antibody via passive immunity test negative later in life due to seroreversion, provided they have never been infected with FIV and have never been immunized with the FIV vaccine.{{citation needed|date=November 2022}}
Cats that have been vaccinated will test positive for the FIV antibody for the rest of their lives owing to seroconversion, even though they are not infected. Therefore, testing of strays or adopted cats is inconclusive, since it is impossible to know whether or not they have been vaccinated in the past. For these reasons, a positive FIV antibody test by itself should never be used as a criterion for euthanasia.<ref>{{Citation| doi = 10.1016/j.jfms.2009.05.006| title = Feline immunodeficiency. ABCD guidelines on prevention and management| year = 2009| author = Hosie, MJ| journal = Journal of Feline Medicine & Surgery| volume = 11| pages = 575–84| pmid = 19481037| issue = 7| postscript = .| display-authors = 1| last2 = Addie| first2 = Diane| last3 = Belák| first3 = Sándor| last4 = Boucraut-Baralon| first4 = Corine| last5 = Egberink| first5 = Herman| last6 = Frymus| first6 = Tadeusz| last7 = Gruffydd-Jones| first7 = Tim| last8 = Hartmann| first8 = Katrin| last9 = Lloret| first9 = Albert | pmc = 7129779}}</ref>
Tests can be performed in a vet's office with results in minutes, allowing for quick consultation. Early detection helps maintain the cat's health and prevents spreading infection to other cats. With proper care, infected cats can live long and healthy lives.<ref>{{cite journal |last1=Ravi |first1=M. |last2=Wobeser |first2=G. A. |last3=Taylor |first3=S. M. |last4=Jackson |first4=M. L. |title=Naturally acquired feline immunodeficiency virus (FIV) infection in cats from western Canada: Prevalence, disease associations, and survival analysis |journal=Canadian Veterinary Journal |volume=51 |issue=3 |pages=271–276 |date=March 2010 |pmid=20514250 |pmc=2822370}}</ref><ref>{{cite journal |last1=Spada |first1=E. |last2=Perego |first2=R. |last3=Sgamma |first3=E. A. |last4=Proverbio |first4=D. |title=Survival time and effect of selected predictor variables on survival in owned pet cats seropositive for feline immunodeficiency and leukemia virus attending a referral clinic in northern Italy |journal=Preventive Veterinary Medicine |volume=150 |pages=38–46 |date=February 2018 |doi=10.1016/j.prevetmed.2017.12.001 |pmid=29406082|hdl=2434/534206 |hdl-access=free }}</ref>
==Treatment options== In 2006, the United States Department of Agriculture issued a conditional license for a new treatment aid termed Lymphocyte T-Cell Immunomodulator (LTCI).<ref>{{Citation|url=http://tcyte.com/ltci-product-info-feline-leukemia/|title=LTCI Product Information|publisher=T-Cyte Therapeutics, Inc.|access-date=28 July 2012|archive-url=https://web.archive.org/web/20120816214812/http://tcyte.com/ltci-product-info-feline-leukemia/|archive-date=16 August 2012|url-status=dead}}</ref> Lymphocyte T-Cell Immunomodulator is manufactured and distributed exclusively by T-Cyte Therapeutics, Inc.<ref name=Label>{{Citation|url=http://www.tcyte.com|title=T-Cyte Therapeutics, Inc.|publisher=T-Cyte Therapeutics, Inc.|access-date=28 July 2012}}</ref>
Lymphocyte T-Cell Immunomodulator is intended as an aid in the treatment of cats infected with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FIV), and the associated symptoms of anemia (reduced oxygen-carrying ability in the blood), opportunistic infection, lymphocytopenia, granulocytopenia, or thrombocytopenia (low levels of lymphocytes, granulocytes, and platelets respectively, the first two are types of white blood cell). The absence of any observed adverse events in several animal species suggests that the product has a very low toxicity profile.{{citation needed|date=November 2022}}
Lymphocyte T-Cell Immunomodulator is a potent regulator of CD-4 lymphocyte production and function.<ref>Beardsley, et al. "Induction of T-Cell Maturation by a Cloned Line of Thymic Epithelium (TEPI) Immunology 80: pp. 6005–6009, (Oct. 1983).</ref> It has been shown to increase lymphocyte numbers and Interleukin 2 production in animals.<ref>{{Ref patent|country=US|number=7196060|inventor=Beardsley, Terry R.|title=Method to enhance hematopoiesis|fdate=2004-09-10|pubdate=2005-05-19|gdate=2007-03-27|status=patent}}</ref> It is a single-chain polypeptide and a strongly cationic glycoprotein, and is purified with cation exchange resin. Purification of protein from bovine-derived stromal cell supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized (freeze-dried) 1 microgram dose. Reconstitution in sterile diluent produces a solution for subcutaneous injection.{{citation needed|date=November 2022}}
==Vaccine== As with HIV, the development of an effective vaccine against FIV is difficult because of the high number of, and differences between, variations of the virus strains. "Single-strain" vaccines, i.e., vaccines that only protect against a single virus variant, have already demonstrated a good efficacy against homologous FIV strains. A dual-subtype vaccine for FIV released in 2002 called Fel-O-Vax made it possible to immunize cats against more FIV strains. It was developed using inactivated isolates of two of the five FIV subtypes (or clades): A Petaluma and D Shizuoka.<ref>{{Citation | doi = 10.1016/j.jfms.2008.03.002| title = 2008 American Association of Feline Practitioners' feline retrovirus management guidelines| year = 2008| author = Levy, J| journal = Journal of Feline Medicine & Surgery| volume = 10| pages = 300–16 | pmid = 18455463 | last2 = Crawford | first2 = C | last3 = Hartmann | first3 = K | last4 = Hofmann-Lehmann | first4 = R | last5 = Little | first5 = S | last6 = Sundahl | first6 = E | last7 = Thayer | first7 = V | issue = 3| doi-access = free | pmc = 10832685 }}</ref> The vaccine was shown to be moderately protective (82% of cats were protected) against subtype A FIV,<ref>{{Citation | last1 = Huang | first1 = C. | last2 = Conlee | first2 = D. | last3 = Loop | first3 = J. | last4 = Champ | first4 = D. | last5 = Gill | first5 = M. | last6 = Chu | first6 = H.J. | year = 2004 | title = Efficacy and safety of a feline immunodeficiency virus vaccine | journal = Animal Health Research Reviews | volume = 5 | pages = 295–300 | doi = 10.1079/AHR200487 | pmid = 15984343 | issue = 2| s2cid = 38671875 }}</ref> but a later study showed it to offer no protection against subtype A.<ref>{{Citation | last1 = Dunham | first1 = S.P. | last2 = Bruce | first2 = J. |last3 = Mackay | first3 = S. | last4 = Golder | first4 = M. |last5 = Jarrett | first5 = O. | last6 = Neil | first6 = J.C. | year = 2006 | title = Limited efficacy of an inactivated feline immunodeficiency virus vaccine | journal = Veterinary Record | volume = 158 | pages = 561–562 | pmid = 16632531 | issue = 16 | doi = 10.1136/vr.158.16.561| s2cid = 37946050 }}</ref> It has shown 100% effectiveness against two different subtype B FIV strains.<ref>{{Citation | last1 = Kusuhara | first1 = H. | last2 = Hohdatsu | first2 = T. | last3 = Okumura | first3 = M. | last4 = Sato | first4 = K. | last5 = Suzuki | first5 = Y. | last6 = Motokawa | first6 = K. | last7 = Gemma | first7 = T. | last8 = Watanabe | first8 = R. | last9 = Huang | first9 = C. | last10 = Arai | first10 = Setsuo | last11 = Koyama | first11 = Hiroyuki | year = 2005 | title = Dual-subtype vaccine (Fel-O-Vax FIV) protects cats against contact challenge with heterologous subtype B FIV infected cats | journal = Veterinary Microbiology | volume = 108 | pages = 155–165 | doi = 10.1016/j.vetmic.2005.02.014 | pmid = 15899558 | issue = 3–4 | display-authors = 8 }}</ref><ref>{{Citation | last1 = Pu | first1 = R. | last2 = Coleman | first2 = J. | last3 = Coisman | first3 = J. | last4 = Sato | first4 = E. | last5 = Tanabe | first5 = T. | last6 = Arai | first6 = M. | last7 = Yamamoto | first7 = JK. | year = 2005 | title = Dual-subtype FIV vaccine (Fel-O-Vax FIV) protection against a heterologous subtype B FIV isolate | journal = Journal of Feline Medicine and Surgery | volume = 7 | pages = 65–70 | doi = 10.1016/j.jfms.2004.08.005 | pmid = 15686976 | issue = 1| s2cid = 26525327 | pmc = 10911555 }}</ref> Vaccination will cause cats to have positive results on FIV tests, making diagnosis more difficult. For these reasons the vaccine is considered "non-core", and the decision to vaccinate should be made after discussion with a veterinarian and consideration of the risks vs. the effectiveness.<ref>{{Citation | doi = 10.1016/j.jfms.2008.03.002| title = 2008 American Association of Feline Practitioners' feline retrovirus management guidelines| year = 2008| author = Levy, J| journal = Journal of Feline Medicine & Surgery| volume = 10| pages = 300–316 | pmid = 18455463 | last2 = Crawford | first2 = C | last3 = Hartmann | first3 = K | last4 = Hofmann-Lehmann | first4 = R | last5 = Little | first5 = S | last6 = Sundahl | first6 = E | last7 = Thayer | first7 = V | issue = 3| doi-access = free | pmc = 10832685 }}</ref>
==Structure== [[File:FIV genome 2013.jpg|thumb|Genome structure of FIV based on available data 2013]]
FIV displays a similar structure to the primate and ungulate lentiviruses. The virion has a diameter from 80 to 100 nanometers and is pleomorphic. The viral envelope also has surface projections that are small, 8 nm, and evenly cover the surface.<ref name="Lecollinet 2007 167–190">{{Citation|last=Lecollinet|first=Sylvie|author2=Jennifer Richardson|title=Vaccination against the feline immunodeficiency virus: The road not taken|journal=Comparative Immunology Microbiology & Infectious Disease|date=12 July 2007|volume=31|issue=2–3|pages=167–190|url=http://www.elsevier.com/locate/cimid|access-date=15 November 2011|doi=10.1016/j.cimid.2007.07.007|pmid=17706778|url-access=subscription}}</ref>
The FIV virus genome is diploid. It consists of two identical single-strands of RNA in each case about 9400 nucleotides existing in plus-strand orientation. It has the typical genomic structure of retroviruses and includes LTR, ''vif'', ''pol'', ''gag'', ''orfA'', ''env'', and ''rev'' genes.<ref name=":2" /><ref name=":4">{{Cite journal|last1=Pecon-Slattery|first1=Jill|last2=McCracken|first2=Carrie L|last3=Troyer|first3=Jennifer L|last4=VandeWoude|first4=Sue|last5=Roelke|first5=Melody|last6=Sondgeroth|first6=Kerry|last7=Winterbach|first7=Christiaan|last8=Winterbach|first8=Hanlie|last9=O'Brien|first9=Stephen J|date=2008|title=Genomic organization, sequence divergence, and recombination of feline immunodeficiency virus from lions in the wild|url= |journal=BMC Genomics|language=en|volume=9|issue=1|page=66|doi=10.1186/1471-2164-9-66|issn=1471-2164|pmc=2270836|pmid=18251995 |doi-access=free }}</ref><ref name=":5">{{Cite journal|last1=Talbott|first1=R. L.|last2=Sparger|first2=E. E.|last3=Lovelace|first3=K. M.|last4=Fitch|first4=W. M.|last5=Pedersen|first5=N. C.|last6=Luciw|first6=P. A.|last7=Elder|first7=J. H.|date=1989-08-01|title=Nucleotide sequence and genomic organization of feline immunodeficiency virus.|journal=Proceedings of the National Academy of Sciences|language=en|volume=86|issue=15|pages=5743–5747|doi=10.1073/pnas.86.15.5743|issn=0027-8424|pmc=297706|pmid=2762293|bibcode=1989PNAS...86.5743T|doi-access=free}}</ref> The Gag polyprotein is cleaved into matrix (MA), capsid (CA) and nucleocapsid (NC) proteins. Cleavage between CA and NC releases a nine amino acid peptide, while cleavage at the C-terminus of NC releases a 2kDa fragment (p2). The Pol polyprotein is translated by ribosomal frame-shifting, a feature shared with HIV. Cleavage of Pol by the viral protease releases the protease itself (PR), reverse transcriptase (RT), deoxyuridine triphosphatase (dUTPase or DU) and integrase (IN). The Env polyprotein consists of a leader peptide (L), surface (SU) and transmembrane (TM) glycoproteins. In common with other lentiviruses, the FIV genome encodes additional short open reading frames (ORFs) encoding the Vif and Rev proteins. An additional short ORF termed ''orfA'' (also known as ''orf2'') precedes the ''env'' gene. The function of OrfA in viral replication is unclear, however the ''orfA''-encoded product may display many of the attributes of HIV-1 accessory gene products such as Vpr, Vpu or Nef.{{citation needed|date=November 2022}}
Among these subtypes, genetic sequences are mostly conserved; however, wide-ranging genetic differences exist between species specific FIV subtypes. Of FIV's genome, ''Pol'' is the most conserved across FIV strains along with ''gag''. On the contrary, ''env'', ''vif'', ''orfa'', and ''rev'' are the least conserved and exhibit the most genetic diversity among FIV strains.<ref name=":6">{{Cite journal|last1=Carpenter|first1=Margaret A.|last2=Brown|first2=Eric W.|last3=MacDonald|first3=D.W.|last4=O'Brien|first4=Stephen J.|date=November 1998|title=Phylogeographic Patterns of Feline Immunodeficiency Virus Genetic Diversity in the Domestic Cat|journal=Virology|language=en|volume=251|issue=2|pages=234–243|doi=10.1006/viro.1998.9402|pmid=9837787|doi-access=free}}</ref>
The capsid protein derived from the polyprotein Gag is assembled into a viral core (the protein shell of a virus) and the matrix protein also derived from Gag forms a shell immediately inside of the lipid bilayer. The Env polyprotein encodes the surface glycoprotein (SU) and transmembrane glycoprotein (TM). Both SU and TM glycoproteins are heavily glycosylated, a characteristic that scientists believe may mask the B-cell epitopes of the Env glycoprotein giving the virus resistance to the virus neutralizing antibodies.<ref name="Lecollinet 2007 167–190"/>
==Lentiviral vector== Like HIV-1, FIV has been engineered into a viral vector for gene therapy.<ref name="Poeschla, E. 1998">{{citation|author-link1=Eric Poeschla |vauthors=Poeschla E, Wong-Staal F, Looney D |year=1998 |title=Efficient transduction of nondividing cells by feline immunodeficiency virus lentiviral vectors |journal=Nature Medicine |volume=4 |issue=3 |pages=354–357 |pmid=9500613 |doi=10.1038/nm0398-354|s2cid=6624732 }}</ref> Like other lentiviral vectors, FIV vectors integrate into the chromosome of the host cell, where it can generate long-term stable transgene expression. Furthermore, the vectors can be used on dividing and non-dividing cells.<ref name="Poeschla, E. 1998"/><ref name="Optimization of Feline Immunodeficiency Virus Vectors for RNA Interference">{{citation |title=Optimization of Feline Immunodeficiency Virus Vectors for RNA Interference |vauthors=Harper SQ, Staber PD, Beck CR, Fineberg SK, Stein C, Ochoa D, Davidson BL |journal=J Virol |date=Oct 2006 |volume=80 |issue=19 |pages=9371–80 |pmid=16973543 |pmc=1617215 |doi=10.1128/JVI.00958-06}}</ref> FIV vectors could potentially be used to treat neurological disorders like Parkinson's disease, and have already been used for transfer RNAi, which may find use as gene therapy for cancer.<ref name="Development and applications of non-HIV-based lentiviral vectors in neurological disorders.">{{citation |title=Development and applications of non-HIV-based lentiviral vectors in neurological disorders |vauthors=Valori CF, Ning K, Wyles M, Azzouz M |journal=Curr Gene Ther |date=Dec 2008| volume=8 |issue=6 |pages=406–18 |pmid=19075624|doi=10.2174/156652308786848030}}</ref>
== Origin and spread == The exact origins and emergence of FIV in felids is unknown; however, studies of viral phylogenetics, felidae speciation, and FIV occurrence alludes to origins in Africa. Analysis of viral phylogenetics shows phylogenetic trees with a starburst phylogenetic pattern which is usually demonstrated by viruses that are a recent emergence with rapid evolution.<ref name=":1">{{Cite journal|last1=Carpenter|first1=M A|last2=Brown|first2=E W|last3=Culver|first3=M|last4=Johnson|first4=W E|last5=Pecon-Slattery|first5=J|last6=Brousset|first6=D|last7=O'Brien|first7=S J|date=1996|title=Genetic and phylogenetic divergence of feline immunodeficiency virus in the puma (Puma concolor).|journal=Journal of Virology|language=en|volume=70|issue=10|pages=6682–6693|doi=10.1128/JVI.70.10.6682-6693.1996|pmid=8794304|pmc=190710|issn=0022-538X|doi-access=free}}</ref> However, differences in topology, branch lengths, high genetic divergence suggest a more ancient origin in felidae species. Fossil records indicate extant felids arose from a common ancestor in Asia approximately 10.8 million years ago, and since then thirty eight species from eight distinct evolutionary lineages have spread and successfully inhabited every continent but Antarctica.<ref name=":2">{{Cite journal|last1=Pecon Slattery|first1=J|last2=O'Brien|first2=S J|date=March 1998|title=Patterns of Y and X chromosome DNA sequence divergence during the Felidae radiation.|journal=Genetics|volume=148|issue=3|pages=1245–1255|doi=10.1093/genetics/148.3.1245|issn=0016-6731|pmc=1460026|pmid=9539439}}</ref> Despite felidae origins in Asia, FIV is absent from felidae species in Asia except for the Mongolian Pallas cat; however, FIV is highly endemic in Africa with four out of five felids having seropositive PCR results.<ref>{{Cite journal|last1=Hofmann-Lehmann|first1=R|last2=Fehr|first2=D|last3=Grob|first3=M|last4=Elgizoli|first4=M|last5=Packer|first5=C|last6=Martenson|first6=J S|last7=O'Brien|first7=S J|last8=Lutz|first8=H|date=September 1996|title=Prevalence of antibodies to feline parvovirus, calicivirus, herpesvirus, coronavirus, and immunodeficiency virus and of feline leukemia virus antigen and the interrelationship of these viral infections in free-ranging lions in east Africa.|journal=Clinical and Diagnostic Laboratory Immunology|volume=3|issue=5|pages=554–562|doi=10.1128/CDLI.3.5.554-562.1996|issn=1071-412X|pmc=170405|pmid=8877134}}</ref> Due to the widespread occurrence and interspecies divergence of FIV strains in Africa, it's suggested that FIV arose in Africa before disseminating worldwide. The high genetic diversity and divergence between FIV strains in African felidae species and the presence of hyena FIV-Ccr, is consistent with a long residence time giving rise to increased opportunities for inter-species transmission among species. Additionally, lentiviruses are also highly endemic in Africa infecting not only felids, but also primates, and ungulate species. This suggests to the origins of all lentiviruses and supports FIV origins in Africa; however, further research is needed.<ref>{{Cite journal|last1=Quérat|first1=G.|last2=Barban|first2=V.|last3=Sauze|first3=N.|last4=Vigne|first4=R.|last5=Payne|first5=A.|last6=York|first6=D.|last7=de Villiers|first7=E.M.|last8=Verwoerd|first8=D.W.|date=May 1987|title=Characteristics of a novel lentivirus derived from South African sheep with pulmonary adenocarcinoma (jaagsiekte)|url=https://linkinghub.elsevier.com/retrieve/pii/0042682287902492|journal=Virology|language=en|volume=158|issue=1|pages=158–167|doi=10.1016/0042-6822(87)90249-2|pmid=2437695|url-access=subscription}}</ref><ref>{{Cite journal|last=Hirsch|first=V|date=December 1995|title=Phylogeny and natural history of the primate lentiviruses, SIV and HIV|url=https://linkinghub.elsevier.com/retrieve/pii/0959437X9580014V|journal=Current Opinion in Genetics & Development|language=en|volume=5|issue=6|pages=798–806|doi=10.1016/0959-437X(95)80014-V|pmid=8745080|url-access=subscription}}</ref>
The spread of FIV from Africa might have occurred during two points of felidae migration. The earliest migration across the Bering Strait into North America occurred approximately 4.5 million years ago during a period of low sea levels.<ref name=":0">{{Cite journal|last=Johnson|first=W. E.|date=2006-01-06|title=The Late Miocene Radiation of Modern Felidae: A Genetic Assessment|url=https://www.science.org/doi/10.1126/science.1122277|journal=Science|language=en|volume=311|issue=5757|pages=73–77|doi=10.1126/science.1122277|pmid=16400146|bibcode=2006Sci...311...73J|s2cid=41672825|issn=0036-8075|url-access=subscription}}</ref> Early felids in North America descended into seven species of the ocelot lineage, two species of the puma lineage, and four of the modern species of lynx.<ref>{{Cite journal|last1=Eizirik|first1=Eduardo|last2=Kim|first2=Jae-Heup|last3=Menotti-Raymond|first3=Marilyn|last4=Crawshaw JR.|first4=Peter G.|last5=O'Brien|first5=Stephen J.|last6=Johnson|first6=Warren E.|date=January 2001|title=Phylogeography, population history and conservation genetics of jaguars (Panthera onca, Mammalia, Felidae)|url=http://doi.wiley.com/10.1046/j.1365-294X.2001.01144.x|journal=Molecular Ecology|language=en|volume=10|issue=1|pages=65–79|doi=10.1046/j.1365-294X.2001.01144.x|pmid=11251788|bibcode=2001MolEc..10...65E |s2cid=3916428|issn=0962-1083|url-access=subscription}}</ref> The most recent migration of Asian lions and jaguars across Eurasia into North and South America occurred during the Pliocene/early Pleistocene.<ref name=":0"/> These migrations events increased opportunities for FIV transmission among felids and established infections globally for felidae species.{{citation needed|date=November 2022}}
== Evolution == === Wild felids === Comparisons of FIV subtypes illustrate rapid evolution and highlights divergence in FIV strains. FIV-Pco, which is specific to American pumas, has two highly divergent subtypes.<ref name=":7">{{Cite journal|last1=Carpenter|first1=M. A.|last2=Brown|first2=E. W.|last3=Culver|first3=M.|last4=Johnson|first4=W. E.|last5=Pecon-Slattery|first5=J.|last6=Brousset|first6=D.|last7=O'Brien|first7=S. J.|date=October 1996|title=Genetic and phylogenetic divergence of feline immunodeficiency virus in the puma (Puma concolor)|journal=Journal of Virology|volume=70|issue=10|pages=6682–6693|doi=10.1128/JVI.70.10.6682-6693.1996|issn=0022-538X|pmc=190710|pmid=8794304}}</ref> Several studies have demonstrated subtypes A and B to have long branch lengths and low geographic similarities which indicates the possibility of two separate FIV introductions into populations coupled with a long residence time.<ref name=":7" /> In the late Pleistocene, pumas fell victim to the ice age, went extinct in North America except for a small inbred population in Florida, and did not re-emerge until 10–12,000 years ago.<ref name=":0"/><ref>{{Cite journal|last1=Antunes|first1=Agostinho|last2=Troyer|first2=Jennifer L.|last3=Roelke|first3=Melody E.|last4=Pecon-Slattery|first4=Jill|last5=Packer|first5=Craig|last6=Winterbach|first6=Christiaan|last7=Winterbach|first7=Hanlie|last8=Hemson|first8=Graham|last9=Frank|first9=Laurence|last10=Stander|first10=Philip|last11=Siefert|first11=Ludwig|date=2008-11-07|editor-last=Estoup|editor-first=Arnaud|title=The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics|journal=PLOS Genetics|language=en|volume=4|issue=11|article-number=e1000251|doi=10.1371/journal.pgen.1000251|issn=1553-7404|pmc=2572142|pmid=18989457 |doi-access=free }}</ref> Phylogenetic analysis of FIV-Pco strains in Central, South, and North America show Central and South American strains are more closely related to North American strains than to each other.<ref name=":7" /><ref name=":8">{{Cite journal|last1=Barr|first1=Margaret C|last2=Zou|first2=Lily|last3=Long|first3=Fan|last4=Hoose|first4=Wendy A|last5=Avery|first5=Roger J|date=February 1997|title=Proviral Organization and Sequence Analysis of Feline Immunodeficiency Virus Isolated from a Pallas' Cat|journal=Virology|language=en|volume=228|issue=1|pages=84–91|doi=10.1006/viro.1996.8358|pmid=9024812|doi-access=free}}</ref> This suggests FIV-Pco was already present in South American pumas which repopulated North America.<ref name=":8" /> <!-- Deleted image removed: thumb|370x370px|Phylogenetic tree of 72 nonidentical FIV strains from 7 carnivore species based on a region of pol - RT (420 bp). --> In African lions, FIV-Ple has diverged in to six subtypes A-F which exhibit distinct geographical endemicity to some degree.<ref>{{Cite journal|last1=Brown|first1=E W|last2=Yuhki|first2=N|last3=Packer|first3=C|last4=O'Brien|first4=S J|date=1994|title=A lion lentivirus related to feline immunodeficiency virus: epidemiologic and phylogenetic aspects.|journal=Journal of Virology|language=en|volume=68|issue=9|pages=5953–5968|doi=10.1128/JVI.68.9.5953-5968.1994|pmid=8057472|pmc=237001|issn=0022-538X|doi-access=free}}</ref> Approximately 2 million years ago, African lions arose and dispersed throughout Africa, Asia, and North, Central, and South America. Modern lions currently reside only on the African continent except for a small population in India.<ref name=":0"/> There is no documented disease association of FIV, but seroprevalence in free- ranging lion populations are estimated to be roughly 90%.<ref>{{Cite journal|last1=Lutz|first1=H.|last2=Isenbügel|first2=E.|last3=Lehmann|first3=R.|last4=Sabapara|first4=R.H.|last5=Wolfensberger|first5=C.|date=December 1992|title=Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus|url=https://linkinghub.elsevier.com/retrieve/pii/016524279290133B|journal=Veterinary Immunology and Immunopathology|language=en|volume=35|issue=1–2|pages=215–224|doi=10.1016/0165-2427(92)90133-B|pmid=1337398|url-access=subscription}}</ref> Phylogenetic analysis of FIV-Ple subtypes A, B, and C show high intra and interindividual genetic diversity and sequence divergence comparable to genetic differences to strains from other Felidae species.<ref name=":4" /> These findings indicate these strains evolved in geographically distant lion populations; however, recent occurrences of these strains within populations in Serengeti National Park suggests recent convergence in the same population.{{citation needed|date=November 2022}}
==== Prevalence in wild felids ==== Feline Immunodeficiency Virus (FIV) is widely distributed across Africa, Asia, North America, South America, and Central America, but it has not been found in Oceania.<ref name=":02">{{Cite journal |last1=Kosugi |first1=Yusuke |last2=Uriu |first2=Keiya |last3=Suzuki |first3=Narumi |last4=Yamamoto |first4=Keisuke |last5=Nagaoka |first5=Shumpei |last6=Kimura |first6=Izumi |last7=Konno |first7=Yoriyuki |last8=Aso |first8=Hirofumi |last9=Willett |first9=Brian J. |last10=Kobayashi |first10=Tomoko |last11=Koyanagi |first11=Yoshio |last12=Ueda |first12=Mahoko Takahashi |last13=Ito |first13=Jumpei |last14=Sato |first14=Kei |date=2021-06-10 |editor-last=Kirchhoff |editor-first=Frank |title=Comprehensive Investigation on the Interplay between Feline APOBEC3Z3 Proteins and Feline Immunodeficiency Virus Vif Proteins |journal=Journal of Virology |language=en |volume=95 |issue=13 |article-number=e0017821 |doi=10.1128/JVI.00178-21 |issn=0022-538X |pmc=8437355 |pmid=33762419}}</ref> The virus affects a majority of species, including lions, hyenas, pumas, leopards, jaguars, bobcats, and tigers.<ref name=":13">{{Cite journal |last1=Broughton |first1=Heather |last2=Govender |first2=Danny |last3=Serrano |first3=Emmanuel |last4=Shikwambana |first4=Purvance |last5=Jolles |first5=Anna |date=2021 |title=Equal contributions of feline immunodeficiency virus and coinfections to morbidity in African lions |journal=International Journal for Parasitology: Parasites and Wildlife |language=en |volume=16 |pages=83–94 |doi=10.1016/j.ijppaw.2021.07.003 |pmc=8385399 |pmid=34466379|bibcode=2021IJPPW..16...83B }}</ref> Currently, FIV has been documented in over nineteen wild felid species due to its transmission through blood and saliva, which often occurs during aggressive interactions.<ref name=":13" /><ref name=":23">{{Cite journal |last1=Roelke |first1=Melody E. |last2=Brown |first2=Meredith A. |last3=Troyer |first3=Jennifer L. |last4=Winterbach |first4=Hanlie |last5=Winterbach |first5=Christiaan |last6=Hemson |first6=Graham |last7=Smith |first7=Dahlem |last8=Johnson |first8=Randall C. |last9=Pecon-Slattery |first9=Jill |last10=Roca |first10=Alfred L. |last11=Alexander |first11=Kathleen A. |last12=Klein |first12=Lin |last13=Martelli |first13=Paolo |last14=Krishnasamy |first14=Karthiyani |last15=O'Brien |first15=Stephen J. |date=2009 |title=Pathological manifestations of feline immunodeficiency virus (FIV) infection in wild African lions |journal=Virology |language=en |volume=390 |issue=1 |pages=1–12 |doi=10.1016/j.virol.2009.04.011 |pmc=2771374 |pmid=19464039}}</ref>
==== Transmission and Susceptibility ==== FIV is more rampant in non-''Panthera'' lineages, such as lynxes, bobcats, cheetahs, and pumas, compared to ''Panthera'' species like lions, leopards, jaguars, and tigers.<ref name=":02" /> Studies indicate that lynxes are more susceptible to FIV due to higher levels of the A3Z3 protein, part of the APOBEC3 family, which limits virus replication in felids. However, A3Z3 mutations do not significantly alter viral genes, suggesting that other genetic or environmental factors may influence the virus's effects.<ref name=":02" />
Members of the ''Panthera'' genus exhibit higher levels of protective protein expression, potentially mitigating the severity of infection.<ref name=":02" /> Additionally, carnivorous diets contribute to FIV transmission, as larger wild felids may contract the virus by consuming smaller, infected prey species, increasing the rates of infection.<ref name=":3">{{Cite journal |last1=Fountain-Jones |first1=Nicholas M. |last2=Kraberger |first2=Simona |last3=Gagne |first3=Roderick B. |last4=Gilbertson |first4=Marie L. J. |last5=Trumbo |first5=Daryl R. |last6=Charleston |first6=Michael |last7=Salerno |first7=Patricia E. |last8=Chris Funk |first8=W. |last9=Crooks |first9=Kevin |last10=Logan |first10=Kenneth |last11=Alldredge |first11=Mathew |last12=Dellicour |first12=Simon |last13=Baele |first13=Guy |last14=Didelot |first14=Xavier |last15=VandeWoude |first15=Sue |date=2022 |title=Hunting alters viral transmission and evolution in a large carnivore |journal=Nature Ecology & Evolution |language=en |volume=6 |issue=2 |pages=174–182 |doi=10.1038/s41559-021-01635-5 |issn=2397-334X |pmc=10111630 |pmid=35087217|bibcode=2022NatEE...6..174F }}</ref><ref name=":23"/>
==== Rise in morbidity ==== Lions infected with FIV show various outcomes. Many live without advanced symptoms, while severe cases are rarely observed in the wild due to rapid mortality or predation. Genetic diversity among FIV strains may influence pathogenicity, similar to how HIV affects humans. Infected lions exhibit reduced T-cell counts, inflammation, and systemic complications, but the disease's progression often occurs beyond reproductive age, limiting its population-level effects.<ref name=":13" />
FIV infections compromise immune function, leading to increased susceptibility to secondary infections and diseases.<ref name=":23" /> Behavioral changes have been observed in infected felids, such as reduced hunting ability and impaired social interactions, may hinder survival.<ref name=":13" /> These behavioral and physiological effects highlight the multifaceted challenges posed by FIV, influenced by genetics, ecological dynamics, and interspecies interactions.<ref name=":23" />
==== Conservation and Species Survival Implications ==== FIV presents a significant but nuanced challenge for wild felids. While it has been connected to immunological complications, current evidence and studies have not conclusively proven that FIV has a significant increase of mortality rates across populations.<ref name=":13" /><ref name=":23" /> However, its effects on individual fitness and survival, driven by genetic susceptibility, ecological interactions, and strain diversity, are undeniable.
A study conducted in Colorado on native puma populations found no definitive correlation between human hunting and the spread of FIV.<ref name=":3" /> Despite this, understanding the complex dynamics of FIV is crucial for effective conservation strategies. The interplay of genetic diversity, environmental factors, and interspecies interactions shapes health outcomes and informs efforts to ensure the survival of affected species<ref name=":23" />
=== Domestic felids === In domestic cats, FIV-Fca is pathogenic and can lead to feline AIDS symptoms and subsequent death. Phylogenetic analysis shows FIV to be a monophyletic branch that diverges into three subtypes A, B, and C.<ref name=":6" /> Domestic cats arose more recently than other felidae species approximately around 10,000 years ago from a subspecies of wildcat ''Felis silvestris'' which inhabited East Asia. Genetic analysis indicates lower genetic diversity of FIV in the domestic cat compared to wild Felidae species, higher evolutionary rates, and higher mortality rates when compared to FIV-Ple and FIV-Pco.<ref>{{Cite journal|last1=Olmsted|first1=R. A.|last2=Hirsch|first2=V. M.|last3=Purcell|first3=R. H.|last4=Johnson|first4=P. R.|date=1989-10-01|title=Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses.|journal=Proceedings of the National Academy of Sciences|language=en|volume=86|issue=20|pages=8088–8092|doi=10.1073/pnas.86.20.8088|issn=0027-8424|pmc=298220|pmid=2813380|bibcode=1989PNAS...86.8088O|doi-access=free}}</ref> This suggests the emergence of FIV in domestic cats was recent since newly emerged viruses tend to have higher evolutionary rates with little to no co-adaption between virus and new host species occurring.<ref name=":6" /> Additionally, seroprevalence studies show companion cats to have a 4–12% occurrence while feral cats have an 8–19% prevalence which is much lower compared to wild felidae species which supports the hypothesis of FIV's recent emergence in this species.<ref>{{Cite journal|last1=Fromont|first1=E.|last2=Pontier|first2=D.|last3=Sager|first3=A.|last4=Jouquelet|first4=E.|last5=Artois|first5=M.|last6=Léger|first6=F.|last7=Stahl|first7=P.|last8=Bourguemestre|first8=F.|date=2000|title=Prevalence and pathogenicity of retroviruses in wildcats in France|url=https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1136/vr.146.11.317|journal=Veterinary Record|language=en|volume=146|issue=11|pages=317–319|doi=10.1136/vr.146.11.317|pmid=10766116|s2cid=34803834|issn=2042-7670|url-access=subscription}}</ref><ref>{{Cite journal|last1=Troyer|first1=Jennifer L.|last2=Pecon-Slattery|first2=Jill|last3=Roelke|first3=Melody E.|last4=Johnson|first4=Warren|last5=VandeWoude|first5=Sue|last6=Vazquez-Salat|first6=Nuria|last7=Brown|first7=Meredith|last8=Frank|first8=Laurence|last9=Woodroffe|first9=Rosie|last10=Winterbach|first10=Christiaan|last11=Winterbach|first11=Hanlie|date=2005-07-01|title=Seroprevalence and Genomic Divergence of Circulating Strains of Feline Immunodeficiency Virus among Felidae and Hyaenidae Species|url= |journal=Journal of Virology|language=en|volume=79|issue=13|pages=8282–8294|doi=10.1128/JVI.79.13.8282-8294.2005|issn=0022-538X|pmc=1143723|pmid=15956574}}</ref>
==Comparison with feline leukemia virus== FIV and feline leukemia virus (FeLV) are sometimes mistaken for one another though the viruses differ in many ways. Although they are both in the same retroviral subfamily (orthoretrovirinae), they are classified in different genera (FeLV is a gamma-retrovirus and FIV is a lentivirus like HIV-1). Their shapes are quite different: FeLV is more circular while FIV is elongated. The two viruses are also quite different genetically, and their protein coats differ in size and composition. Although many of the diseases caused by FeLV and FIV are similar, the specific ways in which they are caused actually differ. Also, while the feline leukemia virus may cause symptomatic illness in an infected cat, an FIV-infected cat can remain completely asymptomatic its entire lifetime.<ref name="Murphy2023">{{cite journal |last1=Murphy |first1=B. G. |last2=Castillo |first2=D. |last3=Mete |first3=A. |title=The Late Asymptomatic and Terminal Immunodeficiency Phases in Experimentally FIV-Infected Cats—A Long-Term Study |journal=Viruses |volume=15 |issue=8 |pages=1775 |date=August 2023 |doi=10.3390/v15081775 |pmid=37632117 |pmc=10457906 |doi-access=free}}</ref>
==See also== * Feline vaccination * Feline coronavirus (FCoV)
==References== === Citations === {{Reflist|30em}}
=== General and cited sources === {{Refbegin}} * {{Citation | last=Johnson | year=2005 | title=Proceedings | url=http://www.ivis.org/proceedings/acvp/2005/Johnson/chapter.asp?LA=1 }} * {{Citation | last=Might | first=Jennifer Lynne | year=2004 | title=Feline Immunodeficiency Virus (FIV) | url=http://www.blackgiraffe.com/jmight/fiv/fiv.html | access-date=2006-01-23 | archive-url=https://web.archive.org/web/20060202182118/http://www.blackgiraffe.com/jmight/fiv/fiv.html | archive-date=2006-02-02 | url-status=dead }} * {{Citation | last=The Lion Research Center | year=2005 | title=FIV in African Lions | url=http://www.lionresearch.org/current_docs/fiv.html | access-date=2008-07-22 | archive-url=https://web.archive.org/web/20080801164128/http://www.lionresearch.org/current_docs/fiv.html | archive-date=2008-08-01 | url-status=dead }} * {{Citation | last=Alley Cat Allies| year=2001 | title=Should we release FIV+ cats? | url=http://www.alleycat.org/document.doc?id=157 | access-date=2014-06-17}} {{Refend}}
==External links== * [http://www.tcyte.com Lymphocyte T-Cell Immunomodulator (LTCI)] * [https://en.wikivet.net/Feline_Immunodeficiency_Virus WikiVet Review Feline Immunodeficiency Virus]
{{Retroviruses}} {{Domestic cat}} {{Taxonbar|from=Q1129598}} {{Authority control}}
{{DEFAULTSORT:Feline Immunodeficiency Virus}} Category:Animal viral diseases Category:Cat diseases Category:Lentiviruses