Modulation of human endogenous retrovirus (HERV) transcription during persistent and de novo HIV-1 infection

作者：Michelle Vincendeau, Ingmar Göttesdorfer, Julia Schreml, Armand G. Ngounou Wetie, Jens Mayer, Alex D. Greenwood, Markus Helfer, S. Krämer, Wolfgang Seifarth, Kamyar Hadian, Ruth Brack‐Werner, Christine Leib‐Mösch · 发表于：Retrovirology · 年份：2015 · DOI：10.1186/s12977-015-0156-6 · 被引用次数：70 · 研究领域：Chromosomal and Genetic Variations、Genetic Mapping and Diversity in Plants and Animals、Genome Rearrangement Algorithms

BACKGROUND: The human genome contains multiple LTR elements including human endogenous retroviruses (HERVs) that together account for approximately 8-9% of the genomic DNA. At least 40 different HERV groups have been assigned to three major HERV classes on the basis of their homologies to exogenous retroviruses. Although most HERVs are silenced by a variety of genetic and epigenetic mechanisms, they may be reactivated by environmental stimuli such as exogenous viruses and thus may contribute to pathogenic conditions. The objective of this study was to perform an in-depth analysis of the influence of HIV-1 infection on HERV activity in different cell types. RESULTS: A retrovirus-specific microarray that covers major HERV groups from all three classes was used to analyze HERV transcription patterns in three persistently HIV-1 infected cell lines of different cellular origins and in their uninfected counterparts. All three persistently infected cell lines showed increased transcription of multiple class I and II HERV groups. Up-regulated transcription of five HERV taxa (HERV-E, HERV-T, HERV-K (HML-10) and two ERV9 subgroups) was confirmed by quantitative reverse transcriptase PCR analysis and could be reversed by knock-down of HIV-1 expression with HIV-1-specific siRNAs. Cells infected de novo by HIV-1 showed stronger transcriptional up-regulation of the HERV-K (HML-2) group than persistently infected cells of the same origin. Analysis of transcripts from individual members of t...