Inhibition of Feline Leukemia Virus Subgroup A Infection by Coinoculation with Subgroup B

Abstract

Feline leukemia virus (FeLV) subgroup B arises de novo through recombination between the env genes of exogenous FeLV subgroup A and endogenous FeLV-like sequences. FeLV-B, which by itself is poorly infectious, will increase to high titer in the presence of FeLV-A, and is associated with FeLV-related neoplastic disease. Although the participation of FeLV-B in disease progression has not been definitively proven, circumstantial evidence supports the hypothesis that the generation of FeLV-B is linked to disease progression. The present study was designed to evaluate whether increasing the levels of FeLV-B early in FeLV-A infection could result in reduction of the incubation period for development of neoplastic disease. For this study, an isolate of FeLV-B, designated FeLV-1B3, was biologically cloned, partially sequenced, and subgroup typed. In in vivo studies, none of the neonatal cats inoculated with FeLV-1B3 alone converted to viremia positive, and all remained healthy throughout the observation period. All of the kittens inoculated with FeLV-A alone became chronically viremic, and those held for long-term observation all developed either neoplastic disease or anemia. However, kittens inoculated with the combination of FeLV-1B3 and FeLV-A showed attenuated infections whereby the majority of cats failed to develop chronic viremia. The apparent interference of FeLV-A infection by FeLV-B was time and titer dependent. This unexpected result suggests that FeLV-B may act as an attenuated virus, causing inhibition of FeLV-A possibly through an immune-mediated mechanism. Partial support for this view was provided by postmortem examination of cats inoculated with FeLV-1B3 alone. Even though none of these cats became viremic, FeLV antigen was detected as focal infections in select tissues, especially salivary gland epithelium, where enough antigen may be expressed to provide an immunizing dose against gag and pol cross-reacting antigens. This work may also provide another approach to vaccine development based on endogenous retrovirus vector systems.

Insertional Polymorphisms of Endogenous Feline Leukemia Viruses

“…Transcription and translation of enFeLVs have also been demonstrated in tissues from healthy cats, including lymphoid tissue, suggesting a protective role for enFeLVs in vivo (7,26). Likewise, inoculation with recombinant subgroup B exogenous FeLV attenuates infection by subgroup A exogenous FeLV (45). By contrast, a protein derived from an enFeLV env region was found to facilitate infection by a T-cell-tropic exogenous FeLV (2).…”

“…As the pathogenesis of feline leukemia involves endogenous FeLVs (2,26,45), enFeLV locus genotypes could be used to assess the relative influences of different enFeLV proviruses on resistance to and progression of exogenous leukemia virus infection or on the types of subgroup B and C viruses generated through recombination. Among domestic cats exposed to exogenous FeLV, some 72% become infected, while 28% remain uninfected (15).…”

“…The degree to which these differing outcomes of feline leukemia virus infection are affected by enFeLVs is uncertain, although truncated envelope proteins derived from enFeLV env regions inhibit infection by exogenous subgroup B feline leukemia viruses (26) or may facilitate infection by a T-cell-tropic exogenous FeLV (2). Furthermore, subgroup B FeLV, which forms after recombination between exogenous and endogenous FeLVs, may attenuate infection with the nonrecombinant virus (45), while the recombinant subgroup C FeLV induces aplastic anemia in infected cats (18). Thus, differences among cats in their genomic enFeLV dispositions may influence the outcome of exposure to or infection with exogenous leukemia viruses.…”

Genetic Characterization of Feline Leukemia Virus from Florida Panthers

“…There are 4 naturally occurring viral subgroups of exogenous FeLV (A, B, C, and T) that are distinguished genetically by sequence differences in the env gene and functionally by receptor interactions required for cell entry (13). FeLV-A is the predominant subgroup circulating in feral cats and is often only weakly pathogenic (14). FeLV-B, -C, and -T subgroups arise in vivo through recombination between exogenous FeLV strains and domestic cat endogenous FeLVs (8,15).…”

Feline Pit2 Functions as a Receptor for Subgroup B Feline Leukemia Viruses

“…In contrast, FeLV-B is found with FeLV-A in some but not all chronically infected cats, and it is very poorly transmitted even at high doses (17,18,40). Both FeLV-B and FeLV-T have been shown to evolve directly from FeLV-A in infected cats (5,8,37,39,42,44,50).…”