Host genes associated with HIV-1 replication in lymphatic tissue

Anthony J. Smith, Qingsheng Li, Stephen W. Wietgrefe, Timothy W. Schacker, Cavan S. Reilly, Ashley T. Haase

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 occurs. 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 (e.g., TCFL5, SOCS5 and SCOS7, KLF10), 2) promote heterochromatin formation (e.g., HIC2, CREBZF, ZNF148/ZBP-89), 3) increase collagen synthesis (e.g., PLOD2, POSTN, CRTAP), and 4) reduce cellular transcription and translation. Potential anti-HIV-1 restriction factors were also identified (e.g., NR3C1, HNRNPU, PACT). Only ∼5% of the transcripts (34) were positively associated with HIV-1 replication. Paradoxically, nearly all of these genes function in innate and adaptive immunity, particularly highlighting heightened gene expression in the IFN 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.

Original languageEnglish (US)
Pages (from-to)5417-5424
Number of pages8
JournalJournal of Immunology
Volume185
Issue number9
DOIs
StatePublished - Nov 1 2010

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Lymphoid Tissue
HIV-1
Genes
Viral Load
Heterochromatin
Groin
Adaptive Immunity
Virus Replication
Innate Immunity
Cultured Cells
Collagen
Lymph Nodes
Cell Proliferation
Viruses
Gene Expression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Smith, A. J., Li, Q., Wietgrefe, S. W., Schacker, T. W., Reilly, C. S., & Haase, A. T. (2010). Host genes associated with HIV-1 replication in lymphatic tissue. Journal of Immunology, 185(9), 5417-5424. https://doi.org/10.4049/jimmunol.1002197

Host genes associated with HIV-1 replication in lymphatic tissue. / Smith, Anthony J.; Li, Qingsheng; Wietgrefe, Stephen W.; Schacker, Timothy W.; Reilly, Cavan S.; Haase, Ashley T.

In: Journal of Immunology, Vol. 185, No. 9, 01.11.2010, p. 5417-5424.

Research output: Contribution to journalArticle

Smith, AJ, Li, Q, Wietgrefe, SW, Schacker, TW, Reilly, CS & Haase, AT 2010, 'Host genes associated with HIV-1 replication in lymphatic tissue', Journal of Immunology, vol. 185, no. 9, pp. 5417-5424. https://doi.org/10.4049/jimmunol.1002197
Smith AJ, Li Q, Wietgrefe SW, Schacker TW, Reilly CS, Haase AT. Host genes associated with HIV-1 replication in lymphatic tissue. Journal of Immunology. 2010 Nov 1;185(9):5417-5424. https://doi.org/10.4049/jimmunol.1002197
Smith, Anthony J. ; Li, Qingsheng ; Wietgrefe, Stephen W. ; Schacker, Timothy W. ; Reilly, Cavan S. ; Haase, Ashley T. / Host genes associated with HIV-1 replication in lymphatic tissue. In: Journal of Immunology. 2010 ; Vol. 185, No. 9. pp. 5417-5424.
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