HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs

• Published in: International journal of molecular sciences Vol. 23; no. 9; p. 4766
• Main Authors: Szojka, Zsófia Ilona, Karlson, Sara, Johansson, Emil, Şahin, Gülşen Özkaya, Jansson, Marianne
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.04.2022; MDPI
• Subjects: Acquired immune deficiency syndrome; AIDS; Amino acids; Antibodies; Asymptomatic; Basic Medicine; Env motifs; Glycoproteins; HIV; HIV-2; Human immunodeficiency virus; Immune system; Infections; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Microbiology in the Medical Area; Mikrobiologi inom det medicinska området; neutralization sensitivity; target cell co-receptors; Viruses; neutralization sensitivity; HIV-2; Env motifs; target cell co-receptors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23094766

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity.