Journal Article

Galectin-8 binds HIV envelope glycoproteins with high affinity and promotes viral infectivity

Karlson, Sara, Nilsson, Ulf J., Sheik-Khalil, Enas, Johansson, Emil, Jansson, Marianne, Kahl-Knutson, Barbro, Leffler, Hakon

2026

Overview

Target cell entry of HIV-1 is dependent on the binding of gp120, the outer component of the viral envelope glycoprotein complex (Env), to CD4 and a coreceptor, preferentially CCR5 or CXCR4. Still, other interactions may also contribute to the infectivity of the virus. One such interaction is between the highly glycosylated gp120 and carbohydrate-binding proteins, such as galectins. Here, we studied the interaction between HIV-1 Env and a panel of galectins and found that galectin-8 (Gal-8), bound with highest affinity (K D < 1µM) and also interacted with soluble CD4. Detailed analysis using probes for different parts of Gal-8 revealed that it was primarily the N-terminal carbohydrate recognition domain that interacted with HIV-1 Env expressing sialylated galactosides and both N- and O-linked glycans. Importantly, in cell cultures Gal-8 enhanced the infectivity of HIV-1, including strains with different coreceptor use and subtype origin, as well as HIV-2. This Gal-8 infectivity enhancement was particularly strong (up to 100-fold) at low virus inoculum doses. Next, we compared Gal-8 infectivity enhancement of primary HIV-1 isolates from people living with HIV at different stages of the infection. Of note, the infectivity of HIV-1 isolates obtained during the chronic, relatively immunocompetent phase, was significantly more enhanced by Gal-8 than isolates obtained at late-stage disease during severe immunodeficiency. Taken together, this study reveals novel carbohydrate dependent interactions between Gal-8 and HIV-1 Env, resulting in enhanced infectivity of HIV-1, with particularly strong effects at low dose exposure of strains circulating during the chronic infection phase. These results suggest that Gal-8 is a cell attachment protein that HIV-1 utilizes for optimized infectivity, which may guide the development of novel intervention strategies targeting this interaction.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: affinity / Anisotropy / Basic Medicine / CD4 / CD4 antigen / CD4 Antigens - metabolism / Cell adhesion / Cell Line / Chronic infection / CXCR4 protein / env Gene Products, Human Immunodeficiency Virus - metabolism / envelope glycoproteins / galectin-8 – HIV interactions / Galectins - metabolism / Glycoprotein gp120 / Glycoproteins / HEK293 Cells / HIV / HIV Envelope Protein gp120 - metabolism / HIV Infections - metabolism / HIV Infections - virology / HIV-1 - metabolism / HIV-1 - pathogenicity / HIV-1 - physiology / HIV-2 - metabolism / HIV-2 - pathogenicity / Human immunodeficiency virus / Humans / Immunodeficiency / Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi) / Immunology in the Medical Area (including Cell and Immunotherapy) / Infections / Infectivity / infectivity enhancement / Inoculum / Lactose / Lectins / Ligands / Medical and Health Sciences / Medicin och hälsovetenskap / Medicinska och farmaceutiska grundvetenskaper / Original Research / Peptides / Polysaccharides / Protein Binding / Proteins / Strains (organisms) / Virus Internalization / Viruses