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. 2024 Jun 29;21(1):148.
doi: 10.1186/s12985-024-02394-y.

Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG

Lindsay Wieczorek  1   2 , David Chang  1   2   3 , Eric Sanders-Buell  1   2 , Michelle Zemil  1   2 , Elizabeth Martinez  1   2 , Jesse Schoen  1   2 , Agnes-Laurence Chenine  1   2   4 , Sebastian Molnar  1   2 , Brittani Barrows  1   2   5 , Kultida Poltavee  6 , Man E Charurat  7 , Alash'le Abimiku  7 , William Blattner  7 , Michael Iroezindu  1   8 , Afoke Kokogho  1   8 , Nelson L Michael  9 , Trevor A Crowell  1   2 , Julie A Ake  1 , Sodsai Tovanabutra  1   2 , Victoria R Polonis  10 ; AFRICOS and TRUST/RV368 Study Groups
Collaborators, Affiliations

Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG

Lindsay Wieczorek et al. Virol J. .

Abstract

The magnitude of the HIV-1 epidemic in Nigeria is second only to the subtype C epidemic in South Africa, yet the subtypes prevalent in Nigeria require further characterization. A panel of 50 subtype G and 18 CRF02_AG Nigerian HIV-1 pseudoviruses (PSV) was developed and envelope coreceptor usage, neutralization sensitivity and cross-clade reactivity were characterized. These PSV were neutralized by some antibodies targeting major neutralizing determinants, but potentially important differences were observed in specific sensitivities (eg. to sCD4, MPER and V2/V3 monoclonal antibodies), as well as in properties such as variable loop lengths, number of potential N-linked glycans and charge, demonstrating distinct antigenic characteristics of CRF02_AG and subtype G. There was preferential neutralization of the matched CRF/subtype when PSV from subtype G or CRF02_AG were tested using pooled plasma. These novel Nigerian PSV will be useful to study HIV-1 CRF- or subtype-specific humoral immune responses for subtype G and CRF02_AG.

Keywords: Antibody; CRF02_AG; Envelope (Env); HIV; Neutralization; Nigeria; Subtype G; West Africa.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Phylogenetic analysis of Nigerian subtype G and CRF02_AG envs. Relationship of HIV-1 subtype G and CRF02_AG env nucleotide sequences with reference subtype envs. Subtype G envs used in this study are represented as dark green (REACH) or light green (AFRICOS) circles. CRF02_AG Envs are dark blue (REACH) or light blue (TRUST/RV368); one env variant is represented for each individual. Subtype G and CRF02_AG reference strains are shown as open circles
Fig. 2
Fig. 2
Antigenic characteristics of Nigerian subtype G and CRF02_AG Envs. A Variable loop length, B) number of potential N-linked glycosylation sites (PNLG), and C) overall charge are shown for subtype G (green) and CRF02_AG (blue) Envs. Statistical differences were determined using Mann Whitney U Test; * = p<0.05, ** = p<0.005, *** = p<0.0005
Fig. 3
Fig. 3
Heat map of the subtype G and CRF02_AG PSV neutralization IC50s compared with reference panel PSV. The IC50s for each NmAb tested against individual participant PSV were used to generate a heat map. The vertical black lines separate the clones for each participant and participant IDs, as well as clone subtypes or CRFs are indicated at the top of the figure. As indicated by the scale, stronger red coloring indicates more potent neutralization, and grey shading denotes not tested
Fig. 4
Fig. 4
Neutralization profiles for subtype G versus CRF02_AG using individual NmAbs. NmAbs targeting the A) MPER, B) V3, C) V1V2, D) CD4bs and E) bridging regions and gp120 glycan were tested against individual PSV and the IC50 values graphed. Statistical differences between Subtype G and CRF02_AG PSV were determined using Mann Whitney U Test; * = p<0.05, ** = p<0.005, *** = p<0.0005, as indicated. F The NmAb GM IC50 was determined for all subtype G and CRF02_AG PSV and plotted to reflect relative NmAb potencies and differences between HIV subtype G and CRF02_AG. The dotted and dashed lines indicate NmAb neutralization potency of GM IC50 = 1 μg/ml or 10 μg/ml, respectively. NmAbs shown in red are potently neutralizing against both subtype G and CRF02_AG; NmAbs shown in yellow were weakly neutralizing against both
Fig. 5
Fig. 5
Cross-clade reactivity of subtype G and CRF02_AG PSV and HIV+ plasma. Plasma pool neutralization was evaluated in the TZMbl neutralization assay against the subtype G and CRF02_AG PSV and reference strains for subtype A, B, C, D and CRF02_AG. Sensitivity to neutralization by plasma pools from pure HIV-1 subtypes/CRFs was determined for all A) subtype G and C) CRF02_AG PSV. Plasma potency was determined against PSVs from different HIV subtypes/CRFs for the B) subtype G and D) CRF02_AG plasma pools. Statistical differences were determined using Mann Whitney U Test; * = p<0.05, ** = p<0.005, *** = p<0.0005
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