Construction of a high titer infectious HIV-1 subtype C proviral clone from South Africa

Viruses. 2012 Sep;4(9):1830-43. doi: 10.3390/v4091830. Epub 2012 Sep 24.

Abstract

The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317.

Keywords: CD317; CD4; HIV-1; Vpu; proviral plasmid; resistance assays; subtype C; viral replication.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Cloning, Molecular
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • HIV-1 / physiology
  • Humans
  • Male
  • Molecular Sequence Data
  • Proviruses / genetics
  • Proviruses / isolation & purification*
  • Proviruses / physiology
  • Sequence Analysis, DNA
  • South Africa
  • Viral Tropism
  • Virus Replication

Substances

  • DNA, Viral

Associated data

  • GENBANK/JN188292