University of Minnesota
University Relations

Minnesota Supercomputing Institute

Log out of MyMSI

Research Abstracts Online
January 2010 - March 2011

Main TOC ...... Next Abstract

University of Minnesota Twin Cities
Medical School
Department of Microbiology

PI: Ashley T. Haase, Associate Fellow

Microarray Analysis of Lymphoidal Tissue During SIV and HIV Infections

Untreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. Although each of the three stages has well-known clinical, virologic, and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. These researchers have used microarray analyses of lymphatic tissue to reveal stage-specific patterns of gene expression during HIV-1 infection. While there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The researchers have also identified genetic factors in vivo that impact viral replication in lymphatic tissue. In order to identify genetic determinants in lymphatic tissue that critically affect HIV-1 replication, they used microarrays to transcriptionally profile and identify host genes expressed in inguinal lymph nodes that were associated determinants of viral load. Strikingly, ~95% of the transcripts (558) in this dataset (592 transcripts total) were negatively associated with HIV-1 replication. Genes in this subset inhibit cellular activation/proliferation, promote heterochromatin formation, increase collagen synthesis, and reduce cellular transcription and translation. Potential anti-HIV-1 restriction factors were also identified. Only ~5% of the transcripts (34) were positively associated with HIV-1 replication. Paradoxically, nearly all these genes function in innate and adaptive immunity, particularly highlighting a heightened interferon system. The researchers have concluded that this conventional host response cannot contain HIV-1 replication and, in fact, could well contribute to increased replication through immune activation. More importantly, genes that have a negative association with virus replication point to target cell availability and potentially new viral restriction factors as principal determinants of viral load. The researchers are now employing a similar approach to examine gene expression in the SIV system to test an experimental vaccine candidate.

Group Members

Qingsheng Li, Research Associate
Anthony Smith, Research Associate
Ming Zeng, Graduate Student