Feline immunodeficiency virus
Feline immunodeficiency virus ( FIV) is a virus from the family of retroviruses. The virus triggers an immune disease in cats, which is referred to as feline immunodeficiency syndrome, or colloquially as feline AIDS because it is very similar to the AIDS disease in humans. However, people can not become infected with FIV. FIV belongs within the retrovirus to the genus of lentiviruses and 1986, ie, described four years after the discovery of the human immunodeficiency virus ( HIV) for the first time. The disease has not effectively treatable, but often runs without symptoms for a long time. In the long term, however, the immune system is destroyed and secondary infections result in death. So far, nine different strains of the virus from eleven different cat species were isolated, including specific strains from lions and pumas. Also in the spotted hyena, which does not belong to the family of cats, FIV has been found. In addition to the feline coronavirus, feline infectious peritonitis, the causative agent of (FIP ) and feline leukemia virus ( FeLV), the causative agent of feline leukemia, the virus is one of the triggers of the most clinically important viral infectious diseases in domestic cats.
- 6.1 Notes and references
- 6.2 Literature
History, distribution and nomenclature
The first FIV virus strains were isolated in 1986 from domestic cats. In a household in Petaluma, California, where many cats lived, there was an outbreak of an immunodeficiency disease. These animals were tested for the feline leukemia virus ( FeLV), but all were negative. It took them blood and injected it into two healthy animals after four to six weeks fever, a decrease in the number of white blood cells ( leukopenia ) and developed a lymph node swelling. From the peripheral blood mononuclear cells ( PBMCs) of these animals was then the first FIV isolated.
Soon after, it was found that serum samples from wild cats such as African lions and cheetahs, Asiatic lions and tigers, jaguars South American and North American Pumas with the antigens of FIV and EIAV, a Pferdelentivirus cross-reacted. These reactions pointed to an infection with FIV. Serological studies of this type (for example, by ELISA ) are still the main way to detect infection with FIV. First, the antigens of the domestic cats were also used for testing the sera of wild cat species. Increases characterization of species-specific antigens of the FIV strains are used, the sensitivity of the test increased considerably. At the same time it was recognized that FI viruses are a large and seen evolutionarily ancient group of retroviruses.
After the first description of North America was gradually detected in domestic cats from around the world also FIV. The worldwide prevalence of FIV - infected domestic cats in the regions and countries is between two and 30 percent. Since the domestic cat was already spread hundreds of years ago from Europe with traders and explorers all over the world, can be assumed that also FIV cats were infected for a long time. Also frozen sera Katz - the oldest tested sera obtained from 1968 from Japan and the U.S. - made positive Serotests. The data on the prevalence vary depending on the pre-selection of the sample material and the population density. Also, large variations occur in different geographic regions. The lions in the Serengeti are practically seropositive to 100 percent, while the lions in Namibia and wild Asian lions are consistently seronegative. Cougars in Wyoming are positive almost 100 percent, while Pumas in Montana are positive only to 20 percent. Because the evolutionary development of lentiviruses is faster than that of cat species, the distribution and similarity of FIV strains allow conclusions to spread, Territories, migration behavior and population dynamics of the different kinds of cats. The collection and analysis of these data is still at the beginning.
The virus with FIV term refers in most cases to isolate from domestic cats. The standard nomenclature for the description of strains from different species is a rear hired symbol, which is composed of the first letter of the genus name and the first two letters of the species name. The FIV of the domestic cat (Felis catus) is therefore also known as FIVfca that of the African lion (Panthera leo ) is called FIVple and Puma concolor FIVpco. The Cougar FIV is sometimes referred to as PLV and lion FIV with LLV, but these two virus strains are in relation to its own name the only exceptions of the nomenclature.
Phylogeny
The previously known FIV strains are highly divergent, but monophyletic, that is the result of a master form. For three of the FIV strains from different animal species subtypes could be determined. The FIV of the domestic cat has been studied the most and has five subtypes that occur worldwide in different frequency and are designated A to E. The division into five sub- groups were by comparing the DNA sequence of the env gene, which encodes the envelope proteins. The subgroups A to C are spread worldwide, D is mainly used in East Asia before and E only in South America.
FIVple by three sub-groups have been determined, labeled A to C. This division was based on sequence differences in the pol gene encodes the viral enzymes (protease, reverse transcriptase and integrase ). At FIVpci two subgroups have been identified and designated as A and B due to differences in pin. The differences in the DNA sequence are considerably between FIV strains in part and are, for example, for the pol gene of FIVple, FIVfca and FIVpco at 30 percent.
The known FIV strains form a separate cluster within the lentiviruses and can be roughly divided into the old and Neuweltspezies. The closest relationship exists with the lentiviruses of cattle and horses.
Construction
FIV is constructed like other lentiviruses that induce immunodeficiency syndromes in mammals. The complete virion has a diameter of 105-125 nanometers is formed spherical or ellipsoidal, and has in the viral envelope short poorly defined projections ( spikes) that gp95 and gp44 consist of the viral glycoproteins. It has, like other retroviruses, a density from 1.15 to 1.17 grams per cubic centimeter. The viral particles are destroyed by conventional alcohol - or chlorine-containing disinfectants and inactivated by a short time (a few minutes ), heating to 60 degrees Celsius.
The viral genome is diploid. It consists of two identical single-stranded nucleotides of in each case about 9400 RNA molecules existing in the positive strand orientation. It has the typical genomic structure of retroviruses consisting of the genes gag-pol - env, and, like other lentiviruses additional ( supplementary) genes. These are vif, vpr and rev. It did lack, vpu, vpx and nef, FIV is therefore less complex than HIV. FIV has Desoxyuridinpyrophosphatase ( dUTPase ) that occurs in the non- primate lentiviruses, and has been described previously except for FIV, and EIAV even for the visna - maedi virus ( VMV ). The dUTPase is encoded in the pol region, the final enzyme degrades dUTP to dUMP and pyrophosphate on what the virus probably helps to prevent incorrect incorporation of dUTP into the genome. From the proviral genome six different splice variants of the mRNA are produced.
Pathogenicity and specificity
The pathogenicity of FIV strains is difficult to determine for cats in the wild. Epidemiological studies in which survival rates were compared with the infection and reproduction rates could not detect any statistically significant disadvantages for the infected animals. Many of the occurring strains can thus be regarded as non-pathogenic. In captivity, however, when the average life expectancy of the animals increased significantly, it comes to the development of disease symptoms. The low pathogenicity of FIV strains in wild cats suggests a long pathogen-host interaction, presumably, as with SIV for about one to two million years ago. In which precursor species to FIV was initially developed is not known. Transfers between different cat species occur in the wild rarely found in captivity are more frequent.
Feline immunodeficiency virus is very host specific, the risk of infection for humans is considered to be minimal. FIV infected, such as HIV -1 primary CD4 T lymphocytes. Compared to HIV-1, one of the two relations occurring in humans, FIV, however, has a slightly wider range of cells, which may infect. In addition to the CD4-positive T cells, monocytes, macrophages, and glial cells, FIV also infects CD8 T and B cells. The primary receptor for the external glycoprotein ( gp95 ) of FIV is not intended, such as in HIV-1 CD4 but CD134. For the interaction between FIV gp95 and CD134 CXCR4 is required as an essential co-receptor. The envelope protein gp95 of the virus binds with its projections (English spikes ) to CD134, which has a conformation change in gp95 results in allowing an interaction with CXCR4. This interaction with the co-receptor stimulates the fusion of the viral envelope with the cell membrane and allows entry into the cell. Since viral strains have been described that do not require CD134, the characterization of the receptors is not yet complete.
It's been successful in a single case to bring the FI virus in human cells or cell lines for propagation. The " block ", ie the barrier that prevents the virus from going through a complete replication cycle, is neither in the cell entry nor in overcoming the nuclear membrane but is that the integrated and detectable in the DNA provirus the critical step of transcription is not more passes. Thus after infection of the cell, no further virus particles can be formed. So that the block is similar to that of EIAV and HIV in human cells in mouse cells.
After initial infection, the virus-specific antibody cat produced immediately and cytotoxic T cells but is not in spite of the severe immune response able to completely overcome the infection. The virus therefore remains in all cases studied so far permanently in the body.
FIV vaccine
Relatively much attention received by the development of an FIV vaccine, which was approved in the U.S. in 2002. It is hoped that the experiences insights for the development of a vaccine against HIV. The development of such a vaccine has been driven since the discovery of the residual virus, and various types of vaccines have been tested, including inactivated virus, virus- infected cells, DNA vaccines and viral vectors. It is unclear whether these services under laboratory conditions, results are reproducible under field conditions with a variety of different FIV strains.
As with HIV, the development of an effective vaccine against FIV due to the high number and variety of virus strains is difficult. For so-called "single strain" vaccines, ie vaccines only protect against a virus occurring variant, a good efficacy against homologous FIV strains has been demonstrated. With the development of a "dual - subtype " FIV vaccine ( Name: Fel -O -Vax FIV) it was possible to immunize cats against other FIV strains. The vaccine consists of inactivated ( killed ) FIV particles of both strains Petaluma subtype A and subtype Shizuoka D. Under laboratory conditions, occurred in 82 percent of cats volunteers immunity against FIV on by the administration of the vaccine. However, a general immunization against primary isolates from the wild appears to be insufficiently possible as before. So far, only a few could also findings from the development of vaccines to be used for the development of an HIV vaccine. The most important criticism of the available vaccine is the fact that vaccinated animals are serologically indistinguishable from infected animals. On the development of a test to distinguish working.
Due to the similar clinical picture and the possibility of immunization, the house cat still plays an increasingly important role in research on HIV and AIDS.
FIV as a viral vector
On the basis of FIV viral vectors for human gene therapy are being developed. As an advantage of FIV thereby missing the disease is seen in humans. FIV vectors are also used in basic research.