HIV-1 sequences isolated from patients promote expression of shorter isoforms of the Gag polyprotein

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• 作者：Christelle Daudé ; Didier Décimo ; Mary-Anne Trabaud ; Patrice André…
• 刊名：Archives of Virology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：161
• 期：12
• 页码：3495-3507
• 全文大小：3,647 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Virology
  Medical Microbiology
  Infectious Diseases
  
• 出版者：Springer Wien
• ISSN：1432-8798
• 卷排序：161

文摘

Human immunodeficiency virus type 1 (HIV-1) unspliced mRNA drives the expression of both Gag and Gag-Pol polyproteins by using both cap- and internal ribosome entry site (IRES)-dependent translation initiation mechanisms. An IRES has been described in the matrix coding region that is involved in the production of shorter isoforms of Gag. However, up to now, this has only been shown with sequences derived from the HIV-1 laboratory strains (NL4.3 and HXB2) and never from clinical HIV-1 isolates. We have isolated ~70 sequences from HIV-1-positive patients that we have sequenced and cloned into an expression vector to monitor their ability to drive translation of Gag p55 and the shorter isoforms both in vitro and ex vivo. The results indicate that (1) the translational efficiency from the AUG-p55 varies significantly among the different isolates; (2) expression initiated at AUG-p40 codon is independent of translation initiation at the AUG-p55 triplet; and (3) all sequences promote expression of shorter Gag isoforms, in particular in Jurkat T cells, in which internal initiation occurs exclusively and directly at the AUG-p40 codon. The composition of the first ~800 nucleotides of the HIV-1 unspliced mRNA modulates the expression initiated both at the AUG-p55 and AUG-p40 codons and may impact viral production and replication. Interestingly, the AUG-p40 codon and its surrounding nucleotide context are conserved amongst clinical isolates and are used as a translation initiation site to produce a shorter Gag isoform.