Hypermutation of HIV-1 DNA in the Absence of the Vif Protein

Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution

“…To detect edited elements, we assumed that a newly edited element should be almost identical to its ancestral element except for a few dense clusters of G-to-A mismatches, as such clusters are the hallmark of APOBEC3 editing [10][11][12][13] . To confirm that the mismatches are due to DNA editing, we exploited the asymmetry, or strand specificity, of editing: as opposed to random mutagenesis, APOBEC3 generates C-to-U mutations specifically on the negative strand of the element (with respect to the ORF), yielding clusters of G-to-A mutations, but not C-to-T, on the positive strand [10][11][12] .…”

“…Occasionally, multiple cytosine-to-uracil deaminations are introduced on the negative-strand retroviral DNA after reverse transcription by proteins of the APOBEC3 (apolipoprotein B mRNA-editing enzyme and catalytic polypeptide 3) family [10][11][12][13] . While encounter with APOBEC3 impairs some viruses, others successfully integrate into the host genome, bearing G-to-A mutations compared with their original sequence.…”

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

“…The molecular nature of permissivity and the exact function of Vif in infection of nonpermissive cells was not known until recently when a series of reports showed that a host cellular protein known as APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G) is a potent inhibitor of HIV infection in the nonpermissive cells [70,71]. APOBEC3G is a member of the cytidine deaminase family, which prevents viral cDNA synthesis via deaminating deoxycytidines (dC) in the minus-strand retroviral cDNA replication intermediate [72][73][74][75][76]. As a result, it creates stop codons or G-A transitions in the newly synthesized viral cDNA which is then subjective to elimination by host DNA repair machinery [74,76].…”

VIH-1 : un virus très Vif !

“…Outre APOBEC1, la famille comprend la protéine AID (activation-induced cytidine deaminase), impliquée dans la production de la diversité des immunoglobulines (➜). Après l'identification d'APOBEC3G, les recherches se sont accélérées, et l'effet antiviral de cette protéine a été caractérisé en quelques mois [2,[4][5][6]. En l'absence de Vif, l'enzyme est incorporée dans les particules virales.…”

“…Ainsi, les levures règlent leur croissance en fonction de la disponibilité en nutriments dans le milieu extracellulaire, via un module de signalisation remarquablement conservé faisant intervenir la protéine kinase TOR (target of rapamycin) [1]. La même kinase TOR est inhibée dans les cellules de mammifères cultivées in vitro lorsqu'elles sont transférées dans un milieu ne contenant pas d'acides aminés, et la synthèse protéique est immédiatement arrêtée [2]. Ces mécanismes de régulation intrinsèques à la cellule sont clairement éta-blis, cependant leur utilisation dans le contexte physiologique de la croissance d'un organisme composé de millions de cellules est encore largement inconnue.…”