Abstract

Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors.

Highlights

  • In many species of Felidae, including the domestic cat, individuals may be infected with a unique strain of feline immunodeficiency virus (FIV), and a related virus is found in African hyenas

  • Viruses isolated from various felid species show monophyletic proviral sequences, Viruses 2011, 3 which supports the idea that FIVs are not frequently transmitted between different felid species [2,3,4]

  • Since FIV infection in domestic cats induces a fatal immunodeficiency that is very similar to AIDS in humans [9,10], FIV infection of cats provides a unique model to investigate the evolutionary role of restriction factors on cross-species transmission, and virus evolution and its impact on AIDS induction

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Summary

Introduction

In many species of Felidae, including the domestic cat, individuals may be infected with a unique strain of feline immunodeficiency virus (FIV), and a related virus is found in African hyenas (for a review, see [1,2]). A group of proteins with potent antiviral properties, known collectively as “restriction factors,” are constitutively expressed in cells, and induced by type I interferon These proteins are able to limit replication by targeting specific steps in the viral life cycle [7]. Vpr inhibits a cellular factor that is still unidentified but, interestingly, Vpx, which is closely related to Vpr (found, for example in Human immunodeficiency virus type 2, HIV-2) is a potent inhibitor of SAMHD1 (see Section 5). Since FIV infection in domestic cats induces a fatal immunodeficiency that is very similar to AIDS in humans [9,10], FIV infection of cats provides a unique model to investigate the evolutionary role of restriction factors on cross-species transmission, and virus evolution and its impact on AIDS induction

FIV and APOBEC3
FIV and TRIM5
FIV and Tetherin
FIV and SAMHD1
Major Challenges in Research on FIV Restriction Factors
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