Feline Syncytium-forming Virus Research Articles

Feline immunodeficiency virus (FIV) infection leads to increased incidence of feline odontoclastic resorptive lesions (FORL)

Feline odontoclastic resorptive lesions (FORL), previously known as `neck lesions,' are commonly known in domestic, but also in non-domestic cats. They are characterized by odontoclastic resorptive processes, which take place at the dental root and at the periodontium. Chronic inflammation of gingiva and periodontium is believed to be an important etiological factor in the development of FORL. In this context, various feline viruses have been discussed to play a relevant role in the pathogenesis of these lesions. The aim of this project was to determine in a blinded study the incidence of FORL in 10 cats which were infected for several years with feline immunodeficiency virus (FIV), but were otherwise free of feline viral infections (feline leukemia virus, feline calicivirus, feline herpesvirus, feline parvovirus, feline coronavirus, feline syncytium-forming virus). Nine age-matched controls were kept under identical conditions, but free of FIV. Subgingival resorptive lesions were found in six of 10 FIV-positive cats, but in three of nine controls only. FIV-positive cats had significantly more often gingivae with an increased tendency for bleeding upon probing than FIV-negative cats ( p=0.0055), and they had slightly more often hyperplastic gingivae ( p=0.0867). In conclusion, signs characteristic of FORL such as subgingival lesions, granulomatous or hyperplastic gingivae with a tendency for bleeding, were found significantly more often in FIV-positive cats than in the controls ( p=0.0198). Therefore, it was concluded that FIV infection is an important factor for the occurrence of FORL, possibly through immune suppression or changes of the (sub)gingival micro-environment. However, non-infected control cats also showed some evidence of FORL in the absence of all tested viral infections. Therefore, factors other than viral infections must also play a role in the development of FORL in cats.

Evaluation of cofactor effect of feline syncytium-forming virus on feline immunodeficiency virus infection

Summary Although feline immunodeficiency virus (fiv) and the unrelated retrovirus feline leukemia virus (FeLV) are associated with acquired immune deficiency in cats, experimental and field evidence indicates that coinfection with both viruses may lead to more serious disease syndrome. A third feline retrovirus, feline syncytium-forming virus (FeSFV), which is far more prevalent than either fiv or FeLV and is considered nonpathogenic in nature, is consistently coisolated from sick, fiv-infected cats. To determine the potential role of FeSFV in enhancement of FIvV-mediated disease, persistent FeSFV infection was established in 14 of 24 nine-month-old cats. Four months later, half the FeSFV-infected and half the noninfected cats were inoculated with blood obtained from a cat persistently infected with the Petaluma strain of fiv. At postinoculation week 17, 1 male cat infected with only fiv died of bacterial bronchopneumonia that could have been attributed to fiv-induced acquired immune deficiency-like syndrome. However, none of the remaining cats had clinical illness, whether infected with either virus alone or coinfected with both viruses. As early as postinoculation week 6, decreases were observed in the CD4+ to CD8+ T-lymphocyte ratio of both groups of cats inoculated with fiv. Infection with FeSFV had no effect on the CD4+ to CD8+ T-cell ratio, Mitogen stimulation assays and total WBC count were unaffected by FeSFV infection, although an increase in numbers of neutrophils from FeSFV-infected cats was consistent, especially when compared with the decrease observed after fiv infection. Overall, results of the study indicate that coinfection with FeSFV may not enhance progression of the fiv-induced early stages of disease and that the positive correlation between FeSFV and fiv-induced acquired immune deficiency-like syndrome is attributable to a common mode of transmission, rather than to a synergistic effect of coinfection.

Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus

An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg 2+-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30 53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic lions were negative for FIV antibodies. Some of the FIV positive lion sera had high antibody titers producing strong bands on Western blot strips even in dilutions of ⪢ 1 : 1000. The Western blot pattern of the lion sera differed from that of domestic cats in that primarily p24 and to a lesser degree p17 was recognized. Antibodies to FeSFV were found in 14 animals (seven with strong, seven with intermediate, reaction). No correlation was found between FIV and FeSFV infection. Antibodies to FeLV were found in two cheetahs which later turned out to have been vaccinated with Leukocell, a FeLV vaccine. Antibodies to EIAV (mainly p26) were found in most but not all of the FIV positive animals. In addition, six out of eight of the Asiatic lions tested had high antibody levels to EIAV p26. Antibodies to VMV p30 were mostly but not exclusively found in sera being positive also for EIAV. From these data it was concluded that a lentivirus antigenically closely related to FIV of domestic cats is widespread in wild felids kept in European zoos. Unsuccessful transmission experiments to SPF cats suggest that the lion virus is highly adapted to its host. Based on the high prevalence in African but not in Asiatic lions it may be postulated that this virus has its origins in Africa. Detection by Western blot of antibodies cross-reacting with EIAV in Asiatic lions seronegative for FIV indicates that there may exist an additional feline lentivirus not recognized so far.

Prevalence of feline immunodeficiency virus and other retroviral infections in sick cats in Italy

Two hundred and seventy-seven sick pet cats living in Italy were tested for antibodies to feline immunodeficiency virus (FIV) and for feline leukemia virus (FeLV) antigen. Overall, 24% of the cats resulted positive for anti-FIV antibody and 18% for FeLV antigen. FIV was isolated from the peripheral mononuclear blood cells of ten out of 15 seropositive cats examined and from one out of eight saliva samples. No FIV isolations were obtained from six serum samples cultured. Feline syncytium forming virus (FeSFV) could be isolated from blood and/or saliva in ten out of 11 FIV seropositive cats examined, in six out of nine FeLV antigen positive cats, in two cats found positive for both infection markers, and in three out of 11 cats negative for both markers. Thus, the probability of isolating FeSFV was enhanced by infection with other exogenous retroviruses.

Detection of feline immunodeficiency proviral DNA in peripheral blood lymphocytes by the polymerase chain reaction

Feline immunodeficiency virus (FIV) proviral DNA was detected by the polymerase chain reaction method (PCR). PCR products were detected by gel electrophoresis and ethidium bromide staining. The P-10, P-15 and P-24 regions of the gag gene of FIV were chosen as the target sequences for amplification, and three primer pairs were prepared. The PCR products subjected to amplification with each primer pair were found to possess sites of digestion by a restriction enzyme, as hypothesized. They did not react with feline leukemia virus (FeLV)-infected or feline syncytium-forming virus (FeSFV)-infected cell-derived DNA, and specifically amplified FIV-infected cell-derived DNA. FIV proviral DNA was detected by the PCR method with either primer pair (one-step amplification: single PCR) in DNA derived from peripheral blood lymphocytes (PBL) from 7 of 12 FIV antibody-positive cats. When PCR products in each of the 12 cats were subjected to a second amplification using the same primer pair (two-step amplification: double PCR), FIV proviral DNA was detected in all of the cats. When PBL samples collected from three cats that were negative and three that were positive in the single PCR were cultured for a few weeks in the presence of interleukin 2, FIV proviral DNA was detected in all six cats by the single PCR method. The results suggest that either the use of cultured PBL as the sample or the performance of the double PCR method enables simple and specific detection of FIV proviral DNA in PBL.

Feline retroviruses: a brief review

Representatives of all three retrovirus subfamilies are recognized in the cat: feline leukaemia virus (an Oncovirus), feline syncytium-forming virus (a Spumavirus) and feline immunodeficiency virus (a Lentivirus). Each of these is briefly reviewed.

Biochemical and immunological characterization of the major structural proteins of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) structural proteins were identified using sera obtained from experimentally inoculated cats. Proteins analysed by both radioimmunoprecipitation and Western blotting were specific for FIV infection and failed to cross-react with either antisera to feline leukaemia virus of feline syncytium-forming virus. Western blot analysis of purified virus revealed immunoreactive proteins with apparent Mr of 65K, 50K, 40K, 32K, 24K, 15K and 10K. The major core structural proteins of the virus were isolated by reverse phase HPLC and the aminoterminal sequences of p10 and p24 were determined. Monoclonal antibodies specific for p24 suggested the presence of a precursor protein that could be detected in 35[S]methionine/cysteine-labelled, virus-infected cell extracts. This putative precursor protein possessed an apparent Mr of 50K (Pr50gag). Further analysis revealed the presence of two additional proteins of 130K and 40K. Experiments utilizing tunicamycin, endoglycosidase H and glycopeptidase F revealed that p130 and p40 exhibited properties characteristic of glycoproteins. Our studies also indicated that FIV is immunologically related to other lentiviruses.

Feline immunodeficiency virus infection

Feline immunodeficiency virus (FIV) (formerly feline T-lymphotropic lentivirus or FTLV) was first isolated from a group of cats in Petaluma, California in 1986. The virus is a typical lentivirus in gross and structural morphology. It replicates preferentially but not exclusively in feline T-lymphoblastoid cells, where it causes a characteristic cytopathic effect. The major structural proteins are 10, 17 (small gag), 28 (major core), 31 (endonuclease?), 41 (transmembrane?), 52 (core precursor polyprotein), 54 62 (reverse transcriptase?), and 110 130 (major envelope) kilodaltons in size. The various proteins are antigenically distinguishable from those of other lentiviruses, although serum from EIAV-infected horses will cross-react with some FIV antigens. Kittens experimentally infected with FIV manifest a transient (several days to 2 weeks) fever and neutropenia beginning 4 to 8 weeks after inoculation. This is associated with a generalized lymphadenopathy that persists for up to 9 months. Most cats recover from this initial phase of the disease and become lifelong carriers of the virus. Complete recovery does not occur to any extent in nature or in the laboratory setting. One experimentally infected cat died from a myeloproliferative disorder several months after infection. The terminal AIDS-like phase of the illness has been seen mainly in naturally infected cats. It appears a year or more following the initial infection in an unknown proportion of infected animals. FIV has been identified in cats from all parts of the world. It is most prevalent in high density populations of free roaming cats (feral and pet), and is very uncommon in closed purebred catteries. Male cats are twice as likely to become infected as females. Older male cats adopted as feral or stray animals are at the highest risk of infection, therefore. The infection rate among freely roaming cats rises throughout life, and reaches levels ranging from less than 1% to 12% or more depending on the area. Clinically affected cats tend to be 5 years or older at the time of hospitalization. Experimental and seroepidemiologic studies suggest that FIV is transmitted mainly by bites. Intimate, non-traumatic contact (mutual grooming, shared use of food, water and litter pans) is inefficient in transmitting the infection. In utero and venereal transmission could not be demonstrated in laboratory settings. There is no statistical linkage between FIV and feline leukemia virus (FeLV) infections in nature. The FeLV infection rate in FIV-infected animals is the same as it is for non-FIV-infected cats. Cats with both infections tend to die more quickly and at a younger age than animals infected with FIV alone. There is a statistical linkage between FIV infection and infection with a third retrovirus of cats, feline syncytium-forming virus (FeSFV). This is probably due to the common mode of transmission of these two retroviruses. The clinical manifestations of terminal FIV infection in nature are varied. One group of cats succumbs over a period of months or years to progressive secondary or opportunistic infections of the oral cavity, upper respiratory tract, gastrointestinal tract, skin, or urinary tract. Others suffer from vague signs of illness, unexplainable anemias, FeLV negative myeloproliferative or lymphoproliferative neoplasms, or neurologic disorders. Neurologic signs are usually of a cortical nature, with dementia and behavioral abnormalities predominating. Similarities between FIV infection of cats and HIV infection of man are striking, making FIV infection of cats a good model for human AIDS. In spite of the similarities between FIV and HIV, there is no evidence that FIV is a health hazard to man or other species of animals.

Feline Syncytium-forming Virus: DNA Provirus Size and Structure

An infectious DNA assay has been used to investigate the size and structure of the genome of feline syncytium-forming virus (FSFV). The dose response between DNA extracted from FSFV-infected cells and plaque number on feline embryo cells followed two-hit kinetics and the mol. wt. of the proviral DNA was estimated as approx. 6 x 10(6).

Feline syncytium-forming virus: identification of a virion associated reverse transcriptase and electron microscopical observations of infected cells.

The maturation of feline syncytium-forming virus (FSFV), a member of the foamy virus sub-family (Spumavirinae), has been studied by electron microscopy of thin sections of infected feline embryo (FEA) cells. The initial event observed was formation of crescent-shaped nucleoids at the plasma membrane. As budding progressed, the nucleoid became circular in outline with an electron-lucent centre in fully mature extracellular particles. These observations suggested that the maturation of FSFV in fully permissive FEA cells resembled that of C-type RNA tumour viruses, rather thant the B-type mouse mammary tumour virus. In this respect FSFV may be distinct from other foamy viruses. However, like other foamy viruses FSFV possessed reverse transcriptase activity. Polymerase activity co-sedimented with infectivity in an equilibrium density gradient and exhibited a preference for poly(rA).oligo(dT)10 over poly(dA).oligo(dT)10 as exogenous template.

Feline syncytium-forming virus proviral DNA Time of synthesis and relationship to the host cell genome

An infectious DNA assay has been used to study the time of synthesis of feline syncytium-forming virus (FSFV) proviral DNA, and also its relationship to the host cell genome. When extracted late in infection, infectious FSFV proviral DNA was associated with high molecular weight DNA with the same buoyant density as host cell DNA. Furthermore, the apparent size of this DNA could be reduced by shearing, suggesting that the fragments containing FSFV provirus also contained sequences not essential for viral replication. These data suggest that the DNA provirus of FSFV was integrated into chromosomal DNA late in infection. Under single-cycle growth conditions, infectious FSFV DNA was detected after 1 hr in the Hirt supernatant and after 2 hr in the Hirt pellet DNA. Progeny virus was not detected until at least 5 hr postinfection. It was concluded that the synthesis of free proviral DNA and its subsequent integration into the host cell genome may be essential events in the replication of foamy viruses.

Infectious DNA from Cells Infected with Feline Syncytium-forming Virus (Spumavirinae)

DNA isolated from cells infected with FSFV (a foamy virus) is infectious when tested on susceptible cells. The virus produced by this infectious DNA is identical to the original infecting virus in terms of plaque and virion morphology and serology.

Infection by feline syncytium-forming virus in Britain.

Infection by feline syncytium-forming virus in Britain.

Intracellular and Extracellular Mineral Crystal Formation Induced by Viral Infection of Cell Cultures

Intracellular mineral crystals were observed in cell cultures infected with one or more feline viruses. One was a feline syncytium-forming virus, and the other was a new feline virus which produced intranuclear inclusions in cell cultures. Crystals were noted both in autogenous cell cultures from trypsinization of kidneys and urinary bladders of infected cats (three passages) and in subcultures of culture fluids from these, made in a stable feline kidney cell line. Free mineral crystals were also noted in the fluids of the cell cultures. In two bladder and two kidney infected autogenous cultures, structures resembling the urinary calculi observed in obstructed cats were seen. These consisted of mineral crystals in a matrix of cellular debris.