Feline immunodeficiency virus

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.^[3] It has since been identified in domestic cats.^[4] It has been suggested FIV originated in Africa and has since spread to feline species worldwide.

Effects

FIV compromises the

Newborn kittens may test positive for up to six months and most thereafter will gradually test negative. It is thought that this is due to antibodies transferred to the kittens via the mother's milk. However these antibodies are transient so subsequent testing will be negative. Once they have received vaccinations against FIV, they will, in the future, always test positive, as the various blood tests detect and show the antibodies that have developed in response to the vaccination.

FIV is known in other feline species, and in fact is

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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 (an organization in the United States), as well as many feral cat organizations, recommends against euthanizing FIV-positive cats, or even spending funds to test for the virus.^[7]

Pathology

The virus gains entry to

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).^[11]

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

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 occurs due to biting being more frequently engaged in by males defending their territory.^[10]

Disease stages

FIV progresses through similar stages to HIV. The initial stage, or acute phase, is accompanied by mild symptoms such as

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.^[13]

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.^{[citation needed]}

Treatment options

In 2006, the

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]}

Lymphocyte T-Cell Immunomodulator is a potent regulator of CD-4 lymphocyte production and function.

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.^[9]

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.^[24][25][26] 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]}

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.^[27]

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.^[9]

Lentiviral vector

Like HIV-1, FIV has been engineered into a viral vector for gene therapy.^[28] 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.^[28][29] 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.^[30]

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.^[31] 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.^[24] 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.^[32] 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.^[33][34]

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.^[35] 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.^[36] The most recent migration of Asian lions and jaguars across Eurasia into North and South America occurred during the Pliocene/early Pleistocene.^[35] These migrations events increased opportunities for FIV transmission among felids and established infections globally for felidae species.^{[citation needed]}

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.^[37] 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.^[37] 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.^[35][38] 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.^[37][39] This suggests FIV-Pco was already present in South American pumas which repopulated North America.^[39] In African lions, FIV-Ple has diverged in to six subtypes A-F which exhibit distinct geographical endemicity to some degree.^[40] 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.^[35] There is no documented disease association of FIV, but seroprevalence in free- ranging lion populations are estimated to be roughly 90%.^[41] 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.^[25] 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]}

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.^[27] 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.^[42] 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.^[27] 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.^[43][44]

Comparison with feline leukemia virus

FIV and

• Feline vaccination

References

Citations