This article reviews the current understanding of retroviral restriction and dependency factors in lentivirus infection. Restriction factors (ie, host proteins that block retroviral infection on the cellular level) are ubiquitous across many mammalian species. By contrast, dependency factors are host or virus features that enable viral replication in the host cell. Lentiviruses have several proteins that can target and neutralize host restriction factors. Host and virus have developed these defenses in somewhat of an evolutionary arms race consistent with the so-called red queen hypothesis. Abrupt changes in restriction or dependency factors over time may explain why lentiviruses—which typically have a very narrow host range—can unexpectedly jump species. A better understanding of restriction factors in nonhuman species may serve as the foundation for the development of gene therapy for HIV-1 in humans. Dogs lack exogenous retroviruses and the restriction and dependency factors of lentiviruses in dogs have yet to be established. Lentiviruses (including HIV-1) have been studied extensively in cats. Cats have 3 exogenous retroviruses (ie, FeLV, FIV, feline foamy virus) as well as many endogenous retroviruses and lack 2 major restriction factors for lentiviruses. This provides a potential window for experimental infection or treatment. Cats also lack the dependency factors for HIV-1 found in humans and some nonhuman primates. These, however, can be provided experimentally through genomic manipulation, making the cat a promising model for HIV-1 susceptibility, treatment, and prevention.

The lack of a robust animal model for HIV-1 infection has certainly slowed the clear elucidation of HIV-1 pathogenicity. This intriguing review, which describes dependency factors and retroviral restriction in lentiviruses, explores the role of restriction factors in pathogenicity. Additional studies and further exploration may have therapeutic implication for many lentiviral infections, including human and feline retroviral infections.—Indu Mani, DVM, DSc (Infectious Disease)

Retroviral restriction and dependency factors in primates and carnivores. Fadel HJ, Poeschla EM. VET IMMUNOL IMMUNOPATHOL 143:179-189, 2011.