Fig 1.
Potential mechanisms for virus resistance to APOBEC-mediated inhibition.
(1) vRNAs selected for the absence of certain sequence motifs prevent APOBEC binding or mutagenesis. (2) Viral genomes may avoid repressive complexes with APOBECs (e.g., A3) that interfere with RNA packaging into virions. (3) Virion proteins that bind to APOBECs may have different consequences including A3 degradation or exclusion from virions. Viral proteins, such as MMTV Rem or HIV-1 Vif, lead to proteasomal degradation of their targeted APOBEC proteins. A3 binding to NC, an abundant viral protein, or foamy virus Bet prevents A3 packaging into virus particles. Virion exclusion of A3 will avoid inhibition of viral replication in target cells. A3 in virions also may be inhibited by binding to polymerases (Pol), such as RT. (4) Selection of viral RNA genomes that have few cytidine residues will provide limited opportunities for APOBEC-mediated mutations. (5) RNRs encoded by gammaherpesviruses, DNA viruses that replicate in the nucleus, block deaminase activity and/or promote the export of A3A and A3B enzymes to the cytoplasm. APOBEC, apolipoprotein B mRNA-editing catalytic polypeptide-like; MMTV, mouse mammary tumor virus; NC, nucleocapsid; RNR, ribonucleotide reductase; RT, reverse transcriptase; vRNA, viral genomic RNA.