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Related Concept Videos

Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...

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Env sequence determinants in CXCR4-using human immunodeficiency virus type-1 subtype C.

Nina H Lin1, Carlos Becerril, Francoise Giguel

  • 1Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.

Virology
|September 8, 2012
PubMed
Summary

This study characterizes rare CXCR4-using HIV-1 subtype C viruses. Key genetic differences in the env gene, particularly the V3 loop, distinguish these viruses from CCR5-using variants, impacting antiretroviral therapy.

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Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Human Immunodeficiency Virus type 1 subtype C (HIV-1C) CXCR4-using viruses are infrequently isolated and poorly understood.
  • Understanding HIV-1C env characteristics is crucial for the clinical application of antiretroviral drugs targeting viral entry.

Purpose of the Study:

  • To characterize the genotypic features of CXCR4-using HIV-1C variants.
  • To identify specific env characteristics that differentiate CXCR4-using from CCR5-using HIV-1C variants.

Main Methods:

  • Phenotyping of 209 env clones from 10 HIV-1C samples for coreceptor usage (CCR5, CXCR4, or dual-tropic).
  • Phylogenetic analysis to assess intra-patient variant clustering.
  • Comparative analysis of amino acid variability, charge, glycosylation sites, and specific substitutions in env clones.

Main Results:

  • Intra-patient CXCR4-using (X4) and CCR5-using (R5) variants formed distinct phylogenetic clusters.
  • X4 envs exhibited greater amino acid variability, insertions, higher net positive charge, fewer glycosylation sites, and increased basic amino acid substitutions in the GPGQ crown compared to R5 envs.
  • Basic amino acid substitution and/or insertion prior to the V3 loop crown were highly sensitive predictors of X4 viruses.

Conclusions:

  • Genotypic characteristics of X4 variants in HIV-1C are distinct from R5 variants.
  • The V3 loop is critical but not always sufficient for CXCR4 utilization.
  • These findings offer insights into HIV-1C tropism and have implications for antiretroviral therapy targeting viral entry.