A naturally occurring bovine APOBEC3 confers resistance to bovine lentiviruses: implication for the co-evolution of bovids and their lentiviruses

Abstract

Mammals have co-evolved with lentiviruses for a long time. As evidence, viral infectivity factor (Vif), encoded by lentiviruses, antagonizes the anti-viral action of cellular APOBEC3 of their hosts. Here, we address the co-evolutionary dynamics of bovine APOBEC3 and the following two bovine lentiviruses: bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV). We determined the sequences of three APOBEC3 genes of bovids belonging to the genera Bos and Bison and showed that bovine APOBEC3Z3 is under a strong positive selection. We found that APOBEC3Z3 of gaur, a bovid in the genus Bos, acquired resistance to JDV Vif-mediated degradation after diverging from the other bovids through conversion of the structural composition of the loop 1 domain. Interestingly, the resistance of gaur APOBEC3Z3 can be attributed to the positive selection of residue 62. This study provides the first evidence, suggesting that a co-evolutionary arms race between bovids and lentiviruses occurred in Asia.

New World feline APOBEC3 potently controls inter-genus lentiviral transmission

“…Sequencing PCR of feline A3Z3 was performed as previously described [ 45 , 46 ]. Briefly, genomic DNA was extracted from the samples described above using the DNA Extractor FM kit (Wako) or the DNeasy Blood & Tissue it (Qiagen).…”

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

“…BIV is distributed worldwide (serological and molecular lines of evidence have been reported in many countries) [ 44 ], whereas JDV is endemic to parts of Indonesia [ 45 ].…”

“…As with sheep, cattle ( Bos taurus , Bt) encode three A3 genes: btA3Z1 , btA3Z2 , and btA3Z3 , and another splicing variant, btA3Z2Z3 [ 163 ]. Only A3Z3 and A3Z2Z3 exhibit a strong anti-lentiviral ability in in vitro cell culture systems [ 146 ] that is counteracted by the BIV and JDV Vif proteins which degrade cattle A3 proteins [ 44 ].…”

“…This result suggests that A3Z1 evolved to escape from Vif-mediated degradation, which might allow it to perform other important biological functions. A3Z3 of gaurs ( Bos gaurus ), another bovid species living in Asia, has been shown to be resistant to JDV Vif-mediated degradation [ 44 ]. Both resistances support the coevolution of bovine and their lentiviruses [ 163 ].…”

Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

“…The A3s restriction factors are likely important to prevent lentiviral transmission between distantly related mammals. The impact of A3s on lentiviral cross-species transmission in more closely related species of a family clade such as primates or felids is only partially understood [ 45 , 79 , 99 , 100 , 131 ]. While some laboratory data on the activity spectrum of different FIV Vifs indicate the potential to counteract A3s of non-autologous Felidae host species, observations in captive or wild animals suggest that FIV cross-species transmission is rare.…”