AI Article Synopsis

  • Nearly all transmitted HIV-1 cases are CCR5 (R5)-tropic, but this research identifies a case of CXCR4 (X4)-tropic HIV-1 in a participant from the RV217 cohort, highlighting its transmissibility.
  • The X4 HIV-1 caused faster depletion of CD4 T cells compared to R5 infections, affecting naive and central memory CD4 subsets more severely, while showing resistance to certain broadly neutralizing antibodies (bNAbs).
  • This study suggests that X4-tropic HIV-1 can be transmitted among individuals with a normal CCR5 gene, indicating that the specific tropism of HIV-1 could influence its transmission potential and

Article Abstract

Background: Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, virus detection and characterization were not at the earliest stages of acute infection.

Methods: We identified an X4-tropic T/F HIV-1 in a participant (40700) in the RV217 acute infection cohort. Coreceptor usage was determined in TZM-bl cell line, NP-2 cell lines, and primary CD4 T cells using pseudovirus and infectious molecular clones. CD4 subset dynamics were analyzed using flow cytometry. Viral load in each CD4 subset was quantified using cell-associated HIV RNA assay and total and integrated HIV DNA assay.

Findings: Participant 40700 was infected by an X4 tropic HIV-1 without CCR5 using ability. This participant experienced significantly faster CD4 depletion compared to R5 virus infected individuals in the same cohort. Naïve and central memory (CM) CD4 subsets declined faster than effector memory (EM) and transitional memory (TM) subsets. All CD4 subsets, including the naïve, were productively infected. Increased CD4 T cell activation was observed over time. This X4-tropic T/F virus is resistant to broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 regions, while most of the R5 T/F viruses in the same cohort are sensitive to the same panel of bNAbs.

Interpretation: X4-tropic HIV-1 is transmissible through mucosal route in people with wild-type CCR5 genotype. The CD4 subset tropism of HIV-1 may be an important determinant for HIV-1 transmissibility and virulence.

Funding: Institute of Human Virology, National Institutes of Health, Henry M. Jackson Foundation for the Advancement of Military Medicine.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533037PMC
http://dx.doi.org/10.1016/j.ebiom.2024.105410DOI Listing

Publication Analysis

Top Keywords

cd4 subset
12
hiv-1
8
tropic hiv-1
8
mucosal route
8
wild-type ccr5
8
ccr5 genotype
8
t/f hiv-1
8
hiv-1 ccr5
8
x4-tropic hiv-1
8
hiv-1 transmissible
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!