the biased nucleotide composition of hiv-1 triggers type i interferon response and correlates with subtype d increased pathogenicityhiv - 1的有偏见的核苷酸组成触发i型干扰素反应和与d亚型致病性的增加.pdf

The Biased Nucleotide Composition of HIV-1 Triggers Type I Interferon Response and Correlates with Subtype D Increased Pathogenicity 1 2 ´ 1 ¨ 3 4 Nicolas Vabret , Marc Bailly-Bechet , Valerie Najburg , Michaela Muller-Trutwin , Bernard Verrier , ´ ´ 1* Frederic Tangy ´ ´ ´ ´ 1 Unite de Genomique Virale et Vaccination, CNRS URA-3015, Institut Pasteur, Paris, France, 2 Laboratoire de Biometrie et Biologie Evolutive, CNRS UMR 5558, Universite ´ ´ ´ ´ Claude Bernard Lyon 1, Villeurbanne, France, 3 Unite de Regulation des Infections Retrovirales, Institut Pasteur, Paris, France, 4 Institut de Biologie et Chimie des Proteines, CNRS FRE 3310, University of Lyon 1, Lyon, France Abstract The genome of human immunodeficiency virus (HIV) has an average nucleotide composition strongly biased as compared to the human genome. The consequence of such nucleotide composition on HIV pathogenicity has not been investigated yet. To address this question, we analyzed the role of nucleotide bias of HIV-derived nucleic acids in stimulating type-I interferon response in vitro. We found that the biased nucleotide composition of HIV is detected in human cells as compared to humanized sequences, and triggers a strong innate immune response, suggesting the existence of cellular immune mechanisms able to discriminate RNA sequences according to their nucleotide composition or to detect specific secondary structures