Conserved residues of the immunosuppressive domain of MLV are essential for regulating the fusion-critical SU-TM disulfide bond

• Published in: Journal of virology Vol. 98; no. 11; p. e0098924
• Main Authors: Hogan, Victoria A., Harmon, Julia, Cid-Rosas, Miguel, Hall, Laura R., Johnson, Welkin E.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 19.11.2024
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Amino Acid Substitution; Animals; Cell Line; Conserved Sequence; Disulfides - metabolism; Editor’s Pick; HEK293 Cells; Humans; Membrane Fusion; Mice; Protein Domains; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Virology; Virus Internalization; Virus-Cell Interactions; fusion; murine leukemia virus; infectivity; gamma-type Env; immunosuppressive domain; envelope glycoprotein
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/jvi.00989-24

The gamma-type Env is a prevalent viral fusogen, found within retroviruses and endogenous retroviruses across vertebrate species and in filoviruses such as Ebolavirus. The fusion mechanism of gamma-type Envs is unique from other Class I fusogens such as those of influenza A virus and HIV-1. Gamma-type Envs contain a hallmark feature known as the immunosuppressive domain (ISD) that has been the subject of some controversy in the literature surrounding its putative immunosuppressive effects. Despite the distinctive conservation of the ISD, little has been done to investigate the role of this region for the function of this widespread fusogen. Our work demonstrates the importance of the ISD for the function of gamma-type Envs in infection, particularly in regulating the intermediate steps of membrane fusion. Understanding the fusion mechanism of gamma-type Envs has broad implications for understanding the entry of extant viruses and aspects of host biology connected to co-opted endogenous gamma-type Envs.