Plant Lectin, MoMo30, Pressures HIV-1 to Select for Variants with Deleted N-Linked Glycosylation Sites

• Published in: Viruses Vol. 17; no. 7; p. 910
• Main Authors: Coleman, Morgan I., Khan, Mahfuz B., Gbodossou, Erick, Diop, Amad, DeBarros, Kenya, Bond, Vincent C., Floyd, Virginia, Kondwani, Kofi, Rice, Valerie Montgomery, Powell, Michael D.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.06.2025; MDPI
• Subjects: Acquired immune deficiency syndrome; AIDS; Anti-HIV Agents - pharmacology; Antiviral agents; CBA; Cell Line; Control; Cucurbitaceae; CXCR4 protein; Cytotoxicity; drug-escalation study; Gene frequency; Glycoprotein gp120; Glycoprotein gp41; Glycoproteins; Glycosylation; gp120; Health aspects; HIV; HIV (Viruses); HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - metabolism; HIV Infections - virology; HIV-1; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 genome MoMo30; Human immunodeficiency virus; Humans; Immune system; Infections; Infectivity; Lectins; Lymphocytes T; Medicinal plants; Mutation; Nucleotide sequence; plant lectin; Plant Lectins - pharmacology; RNA, Viral - genetics; Selection, Genetic; T-Lymphocytes - virology; Testing; Vaccines; Viral envelope proteins; Viral infections; Viruses; β-Galactosidase; United States; United States > US; Chicago Illinois; HIV-1; CBA; Momordica balsamina; drug-escalation study; HIV-1 genome MoMo30; gp120; HIV-1 envelope; plant lectin
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v17070910

Momordica balsamina, a plant traditionally used in African medicine, contains a 30 kDa protein, MoMo30, previously identified by our group as an anti-HIV agent that binds glycan residues on the gp120 envelope protein, thereby acting as an entry inhibitor. In this study, we investigated whether prolonged exposure to MoMo30 exerts selective pressure on HIV-1 and induces mutations in the viral envelope (env) gene. T-lymphocyte cells were infected with HIV-1NL4-3 and continuously treated with MoMo30 over a 24-day period. Viral RNA was isolated at regular intervals, and env genes were sequenced using the Illumina platform. RNA sequence variant calling was performed using iVar, which uses a frequency-based binomial test with a default allele frequency threshold of 3% and a minimum base quality of 20 and applies Bonferroni correction for multiple testing. The infectivity of the MoMo30-exposed virus was assessed using MAGI-CXCR4 cells, visualized by β-galactosidase staining, and compared to untreated controls. Statistical significance was determined via two-way ANOVA. MoMo30-treated HIV-1 exhibited multiple detrimental mutations in gp120 and gp41, including missense, nonsense, and frameshift changes. Notably, 32% of N-linked glycosylation sites were deleted in the treated virus, while no such changes were observed in controls. Functionally, the MoMo30-treated virus demonstrated a sixfold reduction in infectivity compared to untreated HIV-1NL4-3. These findings suggest that MoMo30 imposes genetic pressure on HIV-1NL4-3, selecting for mutations that reduce viral fitness.