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Case Reports
. 2025 Aug 26;1(6):e00101-25.
doi: 10.1128/asmcr.00101-25. eCollection 2025 Nov.

Distinct memory CD4+ T cell subset tropism of two CCR5-tropic HIV-1 in a rapid progressor

Manukumar Honnayakanahalli Marichannegowda  1 , Yasmine Farah  1 , Meera Bose  2   3 , Eric Sanders-Buell  2   3 , David King  3 , Leilani Francisco  2   3 , Leigh Anne Eller  2   3 , Abdur Rashid  4 , Sodsai Tovanabutra  2   3 , Nelson L Michael  5 , Merlin L Robb  2   3 , Hongshuo Song  1   4   6
Affiliations
Case Reports

Distinct memory CD4+ T cell subset tropism of two CCR5-tropic HIV-1 in a rapid progressor

Manukumar Honnayakanahalli Marichannegowda et al. ASM Case Rep. .

Abstract

Background: Low HIV-1 infection level in the central memory CD4+ T cell subset is a hallmark of both non-progressive HIV infection and non-pathogenetic SIV infection in the natural hosts. However, an important gap in knowledge is whether CCR5-tropic HIV-1 variants have different memory CD4+ T cell subset preferences.

Case summary: Here, we identified clear compartmentalization of two CCR5-tropic HIV-1 in different memory CD4+ T cell subsets in a rapid progressor. Participant 40512 was identified in the RV217 cohort. While the transmitted/founder (T/F) virus in 40512 was compartmentalized in the central memory CD4+ T cells, the superinfecting virus was compartmentalized in the effector memory CD4+ T cells. Both viruses rely on CCR5 to infect primary CD4+ T cells. The T/F virus is more than 100-fold more resistant to the CCR5 inhibitor Maraviroc than the superinfecting virus.

Conclusion: This case report demonstrates that CCR5 HIV-1 variants have distinct memory CD4+ T cell subset preferences in vivo. Because CD4+ T cell subset targeting is highly relevant for HIV-1 pathogenesis, understanding the underlying molecular mechanisms may provide deeper insights into HIV-1 therapeutics and functional cure.

Keywords: CCR5; CD4+T cell subset; HIV-1; pathogenesis; tropism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Highlighter plot showing longitudinal virus evolution in participant 40512. The T/F virus (defined as the consensus sequence of day 6) is used as the reference (master) sequence. The superinfecting strain was first detected at day 401. The T/F lineage and the superinfecting lineage at day 401 are color-coded.
Fig 2
Fig 2
(A) CD4 and VL dynamics in 40512. The time frame after superinfection is indicated in yellow. (B) Phylogenetic tree and highlighter plot showing the evolutionary relationship between viruses in plasma and in each CD4+ T cell subset. Different viruses are color-coded in the tree. Viral sequences in the CM, TM, and EM CD4+ T cells are shaded in yellow, blue, and pink, respectively. Viral sequences in each CD+ T cell subset were obtained by two independent experiments.
Fig 3
Fig 3
(A) Coreceptor usage of the T/F virus and the SI strain in a panel of NP-2 cell lines. The experiments were performed in duplicate, and the error bar shows the standard deviation. (B) Virus sensitivity to Maraviroc inhibition in the NP-2 CCR5 cell line. The Maraviroc IC50 of each virus is shown. (C) Virus sensitivity to Maraviroc inhibition in primary CD4+ T cells. The percentage of inhibition for each virus is shown. (D) In vitro CD4+ T cell subset tropism of the T/F virus and the superinfecting virus. The percentage of each CD4+ T cell subset among the total infected cells is shown. The statistical significance is determined by a chi-squared test.
See this image and copyright information in PMC

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