Feline leukemia virus infection: a model of effective retroviral immunity

Abstract

Feline leukemia virus (FeLV) infection is a naturally occurring, horizontally transmitted gammaretrovirus infection of cats that causes cancer and immunosuppression. A substantial fraction of cats exposed to FeLV effectively contain virus and resist induction of persistent antigenemia and viremia. Little is known, however, about the state of the viral genome in these animals. To further explore FeLV:host relationships using more sensitive nucleic acid-based detection methods, we developed a quantitative real-time PCR (qPCR) assay to detect FeLV DNA in blood cells and tissues. This assay allowed us to detect DNA in circulating cells of non-antigenemic cats that had ostensibly resisted viral challenge. Thus, we categorized four FeLV:host relationships in cats exposed to FeLV: 1) undetectable antigenemia and viral DNA; 2) undetectable antigenemia but low viral DNA levels; 3) transient antigenemia and moderate viral DNA levels; and 4) persistent antigenemia and high viral DNA levels. These host:virus relationships were established by 8 weeks post-challenge and were maintained for years. Because viral DNA levels in circulation and tissues were highly correlated, we surmise that exposed cats in which viral DNA was not detectable did not maintain a tissue reservoir. We next sought to determine whether the viral DNA detected was transcriptionally active. Thereby a reverse transcriptase qPCR assay was developed to quantitate extracellular FeLV RNA. We demonstrated an almost perfect agreement and a strong linear relationship between viral DNA and RNA levels, inferring that detected FeLV DNA is both integrated and transcriptionally active. However, only high levels of viral DNA and RNA were associated with detectable infectious virus. Finally, these studies also demonstrated that two whole inactivated virus (WIV) adjuvanted FeLV vaccines provided effective protection against FeLV challenge. In nearly every recipient of these vaccines, neither viral DNA, RNA, antigen, nor infectious virus could be detected in blood. Moreover, effective viral containment occurred despite a weak virus neutralizing antibody response. The above findings extend and reinforce the precept of FeLV infection as a model of the early immune responses that determine effective vs. ineffective containment of retroviral infections, and hold valuable insights into immunoprevention and therapy.