Trends in Molecular Medicine
Research FocusDeath and the retrovirus
Section snippets
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
References (20)
DNA deamination mediates innate immunity to retroviral infection
Cell
(2003)Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif
Cell
(2003)An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22
Genomics
(2002)HIV genetic variation is directed and restricted by DNA precursor availability
J. Mol. Biol.
(1997)Naturally occurring hepatitis B virus genomes bearing the hallmarks of retroviral G→A hypermutation
Virology
(1997)RNA editing: cytidine to uridine conversion in apolipoprotein-B mRNA in vitro
Biochim. Biophys. Acta
(2000)Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein
Nature
(2002)Hypermutation of HIV-1 DNA in the absence of the Vif protein
Science
(2003)Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
Nature
(2003)The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA
Nature
(2003)
Cited by (31)
Lethal mutagenesis of HIV
2005, Virus ResearchUnedited inhibition of HBV replication by APOBEC3G
2004, Journal of HepatologyCytidine deamination of retroviral DNA by diverse APOBEC proteins
2004, Current Biology