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Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...

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Amplifying and Quantifying HIV-1 RNA in HIV Infected Individuals with Viral Loads Below the Limit of Detection by Standard Clinical Assays
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Current methods for detecting and assessing HIV-1 antibody resistance.

Stanley Odidika1,2,3, Martin Pirkl3,4, Thomas Lengauer3,4,5

  • 1Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Frontiers in Immunology
|January 21, 2025
PubMed
Summary

Broadly neutralizing antibodies (bNAbs) show promise for HIV treatment, but HIV-1 antibody resistance (HIVAR) hinders their use. Understanding and detecting HIVAR is crucial for developing effective HIV therapies and vaccines.

Keywords:
HIVaidsantibodybNAbsbroadly neutralizing antibodiesmutation

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Area of Science:

  • Immunology
  • Virology
  • Drug Development

Background:

  • Antiretroviral therapy (ART) remains standard for HIV but faces challenges with adherence and side effects, with millions of new infections and deaths annually.
  • Broadly neutralizing antibodies (bNAbs) offer a promising alternative for HIV-1 treatment and prevention, demonstrating potential in clinical trials.
  • HIV-1 antibody resistance (HIVAR), driven by variants in HIV-1 envelope glycoproteins, is a significant barrier to bNAb efficacy and vaccine development.

Purpose of the Study:

  • To review current methods for detecting, characterizing, and predicting HIV-1 antibody resistance (HIVAR).
  • To highlight the importance of understanding HIVAR for the clinical application of broadly neutralizing antibodies (bNAbs) in HIV treatment and prevention.
  • To identify gaps in current HIVAR detection assays and define resistance for novel bNAbs.

Main Methods:

  • Structural analysis of antibody-HIV-1 Env complexes to identify critical viral residues for neutralization.
  • In vitro viral neutralization and adaptation assays to assess bNAb susceptibility based on envelope sequence.
  • In vivo studies in animal models and clinical trials to observe the emergence of HIVAR variants.

Main Results:

  • Structural, in vitro, and in vivo studies have identified and validated HIVAR for most available bNAbs.
  • Emergence of escape variants to bNAb treatments has been observed in both animal models and human clinical trials.
  • Despite progress, defined assays for HIVAR detection in patients are lacking, and resistance profiles for some novel bNAbs remain undefined.

Conclusions:

  • HIVAR is a critical challenge for the clinical use of bNAbs and the development of effective HIV vaccines.
  • Continued research into structural, in vitro, and in vivo methods is essential for understanding and overcoming HIVAR.
  • Development of standardized diagnostic assays for HIVAR detection is urgently needed to guide bNAb therapy and future vaccine strategies.