Identification of cellular proteins required for replication of human immunodeficiency virus type 1

Natallia Dziuba, Monique R. Ferguson, William A. O'Brien, Anthony Sanchez, Andrew J. Prussia, Natalie J. McDonald, Brian M. Friedrich, Guangyu Li, Michael W. Shaw, Jinsong Sheng, Thomas W. Hodge, Donald H. Rubin, James L. Murray

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Cellular proteins are essential for human immunodeficiency virus type 1 (HIV-1) replication and may serve as viable new targets for treating infection. Using gene trap insertional mutagenesis, a high-throughput approach based on random inactivation of cellular genes, candidate genes were found that limit virus replication when mutated. Disrupted genes (N=87) conferring resistance to lytic infection with several viruses were queried for an affect on HIV-1 replication by utilizing small interfering RNA (siRNA) screens in TZM-bl cells. Several genes regulating diverse pathways were found to be required for HIV-1 replication, including DHX8, DNAJA1, GTF2E1, GTF2E2, HAP1, KALRN, UBA3, UBE2E3, and VMP1. Candidate genes were independently tested in primary human macrophages, toxicity assays, and/or Tat-dependent β-galactosidase reporter assays. Bioinformatics analyses indicated that several host factors present in this study participate in canonical pathways and functional processes implicated in prior genome-wide studies. However, the genes presented in this study did not share identity with those found previously. Novel antiviral targets identified in this study should open new avenues for mechanistic investigation.

Original languageEnglish (US)
Pages (from-to)1329-1339
Number of pages11
JournalAIDS Research and Human Retroviruses
Volume28
Issue number10
DOIs
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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    Dziuba, N., Ferguson, M. R., O'Brien, W. A., Sanchez, A., Prussia, A. J., McDonald, N. J., Friedrich, B. M., Li, G., Shaw, M. W., Sheng, J., Hodge, T. W., Rubin, D. H., & Murray, J. L. (2012). Identification of cellular proteins required for replication of human immunodeficiency virus type 1. AIDS Research and Human Retroviruses, 28(10), 1329-1339. https://doi.org/10.1089/aid.2011.0358