Monkeypox virus A35R protein (A35R)

The Monkeypox virus A35R protein is a transmembrane envelope glycoprotein expressed on the enveloped virion (EV) form of the virus, homologous to vaccinia virus A33R, and plays a critical role in poxvirus replication and pathogenesis. It facilitates the formation of actin-containing microvilli on infected cells, enabling efficient cell-to-cell spread of viral particles, and coordinates incorporation of other viral proteins into EV membranes as part of a complex with OPG162 and OPG190. Loss of A35R results in 1000-fold attenuation of viral virulence, underscoring its importance in infection. In monkeypox disease, A35R contributes to viral transmission and dissemination, making it a key player in orthopoxvirus infections like mpox outbreaks. Recent studies have identified high-affinity human monoclonal antibodies (e.g., EV35-2, EV35-6, EV35-7, mAb981) that bind a highly conserved epitope on A35R, blocking viral spread in vitro and protecting mice from lethal challenge via both Fc-dependent and independent mechanisms; elevated natural A35R-specific antibodies in convalescent sera correlate with better clinical outcomes. Crystal structures of A35R-antibody complexes reveal structural vulnerabilities exploitable for therapies, positioning A35R as a promising therapeutic target for next-generation orthopoxvirus treatments due to its conservation across poxviruses.

Other names

A35 proteinA35OPG161VACV A33R homolog

Neutralization of viral spread via binding to conserved epitope on A35R (Fc-dependent and Fc-independent), Blockade of enveloped virion transmission