Host Genes Associated with HIV-1 Replication in Lymphatic Tissue

Authors

• Anthony J. Smith, University of MinnesotaFollow
• Qingsheng Li, University of MinnesotaFollow
• Stephen W. Wietgrefe, University of MinnesotaFollow
• Timothy W. Schacker, University of Minnesota
• Cavan S. Reilly, University of MinnesotaFollow
• Ashley T. Haase, University of MinnesotaFollow

Document Type

Article

Date of this Version

11-1-2010

Citation

J Immunol. 2010 November 1; 185(9): 5417–5424. doi:10.4049/jimmunol.1002197

Comments

Copyright © 2011 Springer Verlag. Used by permission.

Abstract

Much effort has been spent recently in identifying host factors required for HIV-1 to effectively replicate in cultured human cells. However, much less is known about the genetic factors in vivo that impact viral replication in lymphatic tissue, the primary anatomical site of virus-host interactions where the bulk of viral replication and pathogenesis occur. In order to identify genetic determinants in lymphatic tissue that critically affect HIV-1 replication, we 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 data set (592 transcripts total) were negatively associated with HIV-1 replication. Genes in this subset (1) inhibit cellular activation/ proliferation (ex.: TCFL5, SOCS5 and SCOS7, KLF10), (2) promote heterochromatin formation (ex.: HIC2, CREBZF, ZNF148/ZBP-89), (3) increase collagen synthesis (ex.: PLOD2, POSTN, CRTAP), and (4) reduce cellular transcription and translation. Potential anti-HIV-1 restriction factors were also identified (ex.: NR3C1, HNRNPU, PACT). 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. We conclude 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.