Question: What is the mechanism of action of APOBEC3G cytidine deaminase to inhibit HIV-1 replication?

Context:
APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element
Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis
HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription
The APOBEC3 deoxycytidine deaminase family functions as host restriction factors that can block replication of Vif (virus infectivity factor) deficient HIV-1 virions to differing degrees by deaminating cytosines to uracils in single-stranded (-)HIV-1 DNA. Upon replication of the (-)DNA to (+)DNA, the HIV-1 reverse transcriptase incorporates adenines opposite the uracils, thereby inducing C/G→T/A mutations that can functionally inactivate HIV-1
APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism
Suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4(+) T cells is associated with inhibition of processive reverse transcription as well as excessive cytidine deamination
These proteins exert their suppressive effects through the inhibition of viral reverse transcription as well as the induction of cytidine deamination within nascent viral cDNA
We demonstrate that APOBEC3 proteins impart a profound deficiency to reverse transcription from the initial stages of cDNA synthesis, as well as excessive cytidine deamination (hypermutation) of the DNAs that are synthesized
Without Vif, A3 proteins, particularly APOBEC3G (A3G) and APOBEC3F (A3F), inhibit HIV-1 replication by blocking reverse transcription and/or integration and hypermutating nascent viral cDNA. The molecular mechanisms of this antiviral activity have been primarily attributed to two biochemical characteristics common to A3 proteins: catalyzing cytidine deamination in single-stranded DNA (ssDNA) and a nucleic acid-binding capability that is specific to ssDNA or ssRNA
A host cytidine deaminase, APOBEC3G (A3G), inhibits replication of human immunodeficiency virus type 1 (HIV-1) by incorporating into virions in the absence of the virally encoded Vif protein (Deltavif virions), at least in part by causing G-to-A hypermutation.
APOBEC3F and APOBEC3G cytidine deaminases potently inhibit human immunodeficiency virus type 1 (HIV-1) replication by enzymatically inserting G-to-A mutations in viral DNA and/or impairing viral reverse transcription independently of their deaminase activity

Answer: During reverse transcription, APOBEC3G deaminates dC to dU in nascent minus-strand viral DNA, resulting in G-to-A hypermutation in the plus strand DNA to inhibit replication of HIV-1, due to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. In an additional line of antiviral defense, APOBEC3G induces deamination of the apical loop cytidine of the trans-activation response (TAR) element, a short stem-loop RNA structure required for binding of elongation factors during HIV-1 transcription elongation, resulting in accumulation of short viral transcripts and production of lower amounts of full-length HIV-1 transcripts in Vif-deficient HIV-1-infected cells.