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bioRxiv · 10.64898/2026.11.09.765515

Differential properties of gp120 from HIV-1 group M subtypes A and B

Tamazawa, Y. C.·Suzuki, D. I.·Suzuki, Y. J.·Shults, N. V.
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Abstract

HIV-1 group M subtypes A and B differ substantially in their gp120 sequence. To determine whether these differences contribute to subtype-specific complications, particularly pulmonary arterial hypertension (PAH), rats were injected with gp120 from subtype A or B. Pulmonary artery (PA) remodeling was assessed after four weeks using hematoxylin and eosin (H&E) staining and the Vessel Morphometry Analysis tool by Autona (autona.org). Subtype A gp120 potently increased PA wall thickness and right ventricular hypertrophy. The CD4-binding region of subtype A lacks a stretch of 16 amino acids (V1 N-glycosylation site), and experiments showed stronger binding of subtype B to CD4. Subtype B gp120 contains an RGKV sequence, which resembles the RGKR sequence of the rabies virus glycoprotein G that binds to the nicotinic acetylcholine receptor (nAChR). Subtype A gp120 possesses a KDKK sequence instead. Molecular dynamics simulations indicated that both sites are surface-exposed. Although nAChR is expressed in PA cells and could potentially drive the pronounced effects of subtype A, MD simulations estimated that subtype B gp120 binds more strongly to nAChR. We also noted a single amino acid difference immediately preceding the REKR furin cleavage sequence: glutamate in subtype A versus glutamine in subtype B gp120. Simulations predicted that subtype A gp120 interacts more effectively with furin, and enzyme assays demonstrated that subtype A promotes a positive feedback loop more strongly than subtype B. Thus, HIV-1 gp120 subtype A is more potent in promoting PAH, and the mechanism may involve enhancing furin activity to elevate gp120 levels.

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Tamazawa, Y. C., Suzuki, D. I., Suzuki, Y. J., Shults, N. V.. 2026-11-11. Differential properties of gp120 from HIV-1 group M subtypes A and B. https://doi.org/10.64898/2026.11.09.765515

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