Viremic control and viral coreceptor usage in two HIV-1-infected persons homozygous for CCR5 Δ32

Timothy J Henrich1, Emily Hanhauser, Zixin Hu

  • 1aBrigham and Women's Hospital bHarvard Medical School, Boston, Massachusetts, USA cInfektionsmedizinisches Centrum Hamburg dInfektionsdiagnostik Labor Lademannbogen, Hamburg, Germany eUniversity of California, San Francisco fRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.

Abstract

Insights

Individuals with CCR5(Δ32/Δ32) can be infected by HIV-1 using alternative coreceptors like CXCR6. This finding is crucial for developing new HIV-1 therapies targeting viral transmission and control.

Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • Understanding HIV-1 transmission and control is vital for developing curative therapies.
  • CCR5 is a key coreceptor for HIV-1 entry, and CCR5(Δ32/Δ32) individuals are generally protected.
  • Efforts to develop HIV-1 curative therapies focus on modifying or disrupting CCR5 expression.

Purpose of the Study:

  • To investigate viral and immune factors in HIV-1 transmission and control among individuals lacking functional CCR5.
  • To determine coreceptor usage of infecting HIV-1 strains in CCR5(Δ32/Δ32) individuals.
  • To explore HIV-1 evolution and immune responses in the context of alternative coreceptor usage.

Main Methods:

  • Identified two HIV-infected CCR5(Δ32/Δ32) individuals with spontaneous HIV-1 control.
  • Determined coreceptor usage of infecting viruses through phenotypic assays.
  • Analyzed genetic evolution of HIV-1 envelope sequences and assessed immune responses.

Main Results:

  • Both participants maintained low viremia and preserved CD4(+) T-cell counts without antiretroviral therapy.
  • One participant was infected by minority X4 virus, while the predominant viral population used CCR5.
  • The second participant's virus utilized alternative coreceptors, such as CXCR6, for entry.

Conclusions:

  • HIV-1 can infect individuals lacking functional CCR5 by utilizing minority X4 variants or alternative coreceptors.
  • Viruses can bypass CCR5 and CXCR4 by engaging other coreceptors for HIV-1 infection.
  • This highlights novel pathways for HIV-1 transmission and potential targets for therapeutic interventions.

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