A family of polynucleotide cytidine deaminases (CDA) that play important roles
A family of polynucleotide cytidine deaminases (CDA) that play important roles in antiviral defence. Human APOBEC3G and 3F can block the replication of a wide array of exogenous retroelements, including retroviruses such as human immunodeficiency virus (HIV) and murine leukaemia virus (MLV) [1,2], and hepadnaviruses such as hepatitis B virus (HBV) [3,4]. Primate lentiviruses including HIV counter APOBEC3G and 3F via their Vif protein, which binds to and triggers the proteasomal degradation of these cellular antivirals. In the absence of Vif, APOBEC3G and -F arepackaged into retroviral particles, and lethally edit nascent viral reverse transcripts [1,2,5,6]. What tethers APOBEC proteins to GS-5816 cost virions has so far remained incompletely characterized. While some have invoked a role for the viral genomic RNA, more undisputed is the claimed importance of the nucleocapsid region of HIV-1 Gag and of yet unknown cellular RNAs in this process [7-14]. APOBEC family members can also act on endogenous substrates, notably retroelements. APOBEC3A, 3G and 3F can block the propagation of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26080418 endogenous retroviruses such as intracisternal-A particles (IAP) [15,16] or MusD,Page 1 of(page number not for citation purposes)Retrovirology 2008, 5:http://www.retrovirology.com/content/5/1/and APOBEC3A, 3B and, to a lesser extent, 3C and 3F can inhibit LINE-1 (Long Interspersed Nuclear Element 1) retrotransposition [15,17-20]. Furthermore, APOBEC3A, APOBEC3B, APOBEC3C and APOBEC3G can prevent Alu retrotransposition, a process mediated in trans by the reverse transcriptase and integrase activities encoded by LINE [17,18]. Interestingly, APOBEC3G overexpression appears to recruit Alu RNAs into APOBEC3G-containing high molecular mass ribonucleoprotein complexes [21]. The Alu family of repetitive sequences is one of the most successful groups of mobile genetic elements, having multiplied to more than one million copies in the human genome in some 65 million years of primate evolution [22,23]. Interestingly, the emergence of Alu as major primate genome remodelers has coincided with the expansion of the APOBEC3 gene family long before the appearance of modern lentiviruses [24,25], and there is a striking evolutionary coincidence between the expansion of the APOBEC gene cluster and the abrupt drop in retrotransposon activity that took place in primates, compared with rodents [26]. While the functions of Alu repetitive elements remain largely unknown, sequence analyses indicate that they originated from the evolutionary conserved 7SL RNA gene [27]. This gene encodes for the approximately 300-nucleotide-long RNA moiety of the signal recognition particle (SRP), a cytoplasmic ribonucleoprotein complex that associates with ribosomes to mediate the translocation of nascent proteins into the endoplasmic reticulum [28]. Interestingly, 7SL RNA was amongst the first host RNAs detected in avian and murine retroviral particles [29,30] and is packaged in HIV-1 virions at ten thousand and seven fold molar excess over the actin mRNA and viral genomic RNA respectively [31]. A recent study points to 7SL RNA as a mediator of APOBEC3G packaging into HIV virions PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27486068 [32]. The results of the present work rather support a model in which the interaction between 7SL RNA and APOBEC3G may shed light on APOBEC3G-mediated inhibition of Alu retrotransposition, but does not mediate the retroviral particle incorporation of the CDA.ing the human APOBEC3G cDNA. The resulting proteins correspond to the NP_004891 an.
