CIB1 and CIB2 are HIV-1 helper factors involved in viral entry

Sci Rep. 2016 Aug 4;6:30927. doi: 10.1038/srep30927.

Abstract

HIV-1 relies on the host-cell machinery to accomplish its replication cycle, and characterization of these helper factors contributes to a better understanding of HIV-host interactions and can identify potential novel antiviral targets. Here we explored the contribution of CIB2, previously identified by RNAi screening as a potential helper factor, and its homolog, CIB1. Knockdown of either CIB1 or CIB2 strongly impaired viral replication in Jurkat cells and in primary CD4+ T-lymphocytes, identifying these proteins as non-redundant helper factors. Knockdown of CIB1 and CIB2 impaired envelope-mediated viral entry for both for X4- and R5-tropic HIV-1, and both cell-free and cell-associated entry pathways were affected. In contrast, the level of CIB1 and CIB2 expression did not influence cell viability, cell proliferation, receptor-independent viral binding to the cell surface, or later steps in the viral replication cycle. CIB1 and CIB2 knockdown was found to reduce the expression of surface molecules implicated in HIV-1 infection, including CXCR4, CCR5 and integrin α4β7, suggesting at least one mechanism through which these proteins promote viral infection. Thus, this study identifies CIB1 and CIB2 as host helper factors for HIV-1 replication that are required for optimal receptor-mediated viral entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Proliferation
  • Cell Survival
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Jurkat Cells
  • RNA, Small Interfering / genetics
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / metabolism
  • Virus Internalization
  • Virus Replication

Substances

  • CCR5 protein, human
  • CIB1 protein, human
  • CIB2 protein, human
  • CXCR4 protein, human
  • Calcium-Binding Proteins
  • RNA, Small Interfering
  • Receptors, CCR5
  • Receptors, CXCR4