New World feline APOBEC3 potently controls inter-genus lentiviral transmission

Abstract

BackgroundThe apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals.ResultsHere we address the co-evolutionary relationship between two New World felids, the puma (Puma concolor) and the bobcat (Lynx rufus), and their lentiviruses, which are designated puma lentiviruses (PLVs). We demonstrate that PLV-A Vif counteracts the antiviral action of APOBEC3Z3 (A3Z3) of both puma and bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The species specificity of PLV-B Vif is irrespective of the phylogenic relationships of feline species in the genera Puma, Lynx and Acinonyx. We reveal that the amino acid at position 178 in the puma and bobcat A3Z3 is exposed on the protein surface and determines the sensitivity to PLV-B Vif-mediated degradation. Moreover, although both the puma and bobcat A3Z3 genes are polymorphic, their sensitivity/resistance to PLV Vif-mediated degradation is conserved.ConclusionsTo the best of our knowledge, this is the first study suggesting that the host A3 protein potently controls inter-genus lentiviral transmission. Our findings provide the first evidence suggesting that the co-evolutionary arms race between lentiviruses and mammals has occurred in the New World.Electronic supplementary materialThe online version of this article (10.1186/s12977-018-0414-5) contains supplementary material, which is available to authorized users.

Expression of APOBEC3 Lentiviral Restriction Factors in Cats

“…Since previous studies indicate that A3 proteins likely play a role in limiting and controlling PLV infection of domestic cats [53,66], these findings suggest that constitutive, rather than regulated levels of cat A3 can be sufficient to inhibit lentiviral cross-species infection. Lentiviral Vif may evolve to counter A3 restriction, resulting in competent infection and enhanced virulence, so the ultimate outcome of an evolutionary conflict between cat A3 and a non-adapted FIV is dependent upon both host and viral adaptation [16,45,67]. Even in the case of a host-adapted lentivirus, there is likely a dynamic balance between A3-mediated restriction and Vif-mediated protection.…”

The Battle between Retroviruses and APOBEC3 Genes: Its Past and Present

“…This observation suggests the possibility that bobcats intrinsically have species barrier(s) that restrict PLV-B infection. Konno et al showed that puma and bobcat APOBEC3Z3 proteins (the orthologs of human APOBEC3H) can be antiviral [ 56 ]. Intriguingly, puma APOBEC3Z3 protein is degraded by both the PLV-A and PLV-B Vif proteins, while bobcat APOBEC3Z3 protein is degraded by PLV-A Vif but is resistant to PLV-B Vif [ 56 ].…”

“…Konno et al showed that puma and bobcat APOBEC3Z3 proteins (the orthologs of human APOBEC3H) can be antiviral [ 56 ]. Intriguingly, puma APOBEC3Z3 protein is degraded by both the PLV-A and PLV-B Vif proteins, while bobcat APOBEC3Z3 protein is degraded by PLV-A Vif but is resistant to PLV-B Vif [ 56 ]. These findings suggest that the cross-species transmission of PLV-B from pumas to bobcats can be hampered by bobcat APOBEC3Z3 protein.…”

Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses

“…Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif–A3 interaction may help to determine the co-evolutionary history of cross-species lentiviral transmission in mammals [ 151 ]. In most cases, the interaction of Vif with A3 proteins is species-specific [ 152 ], but some lentiviral Vif proteins are capable of triggering the degradation of A3 proteins of several other mammals in addition to their natural host species [ 153 ].…”

“…However, differences are seen, as puma lentiviruses group A (PLV-A) counteract the antiviral action of A3Z3 of both puma and bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The amino acid at position 178 in the puma and bobcat A3Z3 is exposed on the protein surface, and determines the sensitivity to PLV-B Vif-mediated degradation [ 151 ].…”