<unk>  has been widely studied and several mechanisms that negatively affect HIV-1 replication have been identified. Cytidine deamination and hypermutation Figure 2: “The mechanism of cytidine deamination by direct nucleophilic attack at position 4 of the pyrimidine ring. This mechanism has been proposed for bacterial cytidine deaminase, an enzyme that shows homology to APOBEC1 and activation-induced deaminase (AID) in the vicinity of the nucleotide or Zn2+ binding region.” Because<unk>  can acts as an AID and is a member of the APOBEC superfamily like APOBEC1, it is likely that a similar mechanism is mediated by<unk>  for cytidine deamination.<unk>  and other proteins in the same family are able to act as activation-induced (cytidine) deaminases (AID).<unk>  interferes with reverse transcription by inducing numerous deoxycytidine to deoxyuridine mutations in the negative strand of the HIV DNA primarily expressed as complementary DNA (cDNA) in a 3’->5’processive manner. Because<unk>  is part of the APOBEC superfamily and acts as an AID, it is likely that the mechanism mediated by<unk>  for cytidine deamination is similar to that of an E. coli cytidine deaminase that is known to be highly homologous to APOBEC1 and AID around the nucleotide and zinc-binding region. The predicted deamination reaction is driven by a direct nucleophilic attack on position 4 of the cytidine pyrimidine ring by the zinc-coordinated enzyme. Water is needed as a source of both a proton and hydroxyl group donor (Figure 2). The deamination (and resulting oxidation) at position 4 yields a carbonyl group and results in a change from cytidine to uridine. The deamination activity ultimately results in G→A hypermutations at “hot spots” of the proviral DNA. Such hypermutation ultimately destroys the coding and replicative capacity of the virus, resulting in many nonviable virions.<unk>  has a much weaker antiviral effect when its active site has been mutated to the point that the protein can no longer mutate retroviral DNA. It was originally thought that the<unk> -mediated deamination can also indirectly lead to viral DNA degradation by DNA repair systems attracted to the mutated residues. However, this has been discounted because human<unk>  reduces viral cDNA levels independently of DNA repair enzymes UNG and SMUG1. Interference with reverse transcription<unk>  interferes with reverse transcription of HIV-1 independent of DNA deamination. tRNA3Lys typically binds to the HIV-1 primer binding site to initiate reverse transcription.<unk>  can inhibit tRNA3Lys priming, thereby negatively affecting viral ssDNA production and virus infectivity. It is predicted that reverse transcription is also negatively affected by<unk>  binding to viral RNA and causing steric alterations. Interference with viral DNA integration<unk>  was associated with interference of viral DNA integration into the host genome in a manner dependent on functional catalytic domains and deaminase activity. Mbisa et al. saw that<unk>  interferes with the processing and removal of primer tRNA from the DNA minus strand, thus leading to aberrant viral 3’ long terminal repeat (LTR) DNA ends. These viral DNA ends are inefficient substrates for integration and plus-strand DNA transfer. As a result, HIV-1 provirus formation is inhibited.
APOBEC3G
GP1BA
GP1BB
PHKA2
PIM2
TOFI
CoWIN
STAR*D