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Death and the retrovirus

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Abstract

A flurry of new papers has shown that HIV reverse transcription is vulnerable to G→A hypermutation. Apparently, cytidine bases in nascent DNA synthesis are lethally edited by the host cell molecule apolipoprotein B editing complex protein (APOBEC) 3G. This death mechanism is circumvented by the HIV viral infectivity factor protein, which prevents APOBEC3G from entering the virion.

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G→A hypermutation

Let us return to HIV, bearing in mind that the APOBEC proteins are involved in cytidine deamination. The phenomenal genetic variation of HIV is well established, although one of the more singular traits is G→A hypermutation – that is monotonous substitution of guanine residues for adenine when compared with the positive (mRNA) strand [10]. In some hypermutated segments, up to 60% of guanine residues can be substituted. Furthermore, hypermutation can occur throughout full-length genomes, in

Hepatitis B virus too

G→A hypermutation is related not only to the classical retroviruses already mentioned but also to human hepatitis B virus (HBV). The HBV virion harbours a DNA genome. Despite this, there is an obligatory reverse transcription step from full-length genomic RNA to DNA within the viral capsid structure in the cytoplasm. To date, there is a single report of two highly G→A hypermutated sequences derived from the serum of one patient [14]. The sequences show all the traits of classical retroviral G→A

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