Evasion of a Human Cytomegalovirus Entry Inhibitor with Potent Cysteine Reactivity Is Concomitant with the Utilization of a Heparan Sulfate Proteoglycan-Independent Route of Entry

• DOI: 10.1128/jvi.02012-19
• Publication Date: 2020-01-14T13:16:40Z
• Authors: M. J. Murray; N. I. Bonilla-Med...; Q. L. Lee; S. J. Oxenford; R. Angell; D. P. Depledge; M. B. Reeves
• Keywords: DIDS

Human cytomegalovirus (HCMV) is major pathogen of nonimmunocompetent individuals that remains in need new therapeutic options. Here, we identify a potent antiviral compound (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid [DIDS]), its mechanism action, and the chemical properties required for activity. In doing so, data argue cysteine-reactive compounds could have capacity to be developed anti-HCMV Importantly, show entry DIDS-resistant virus became independent heparan sulfate proteoglycans (HSPGs) but, concomitantly, more sensitive neutralizing antibody responses. This serendipitous observation suggests retention an interaction with HSPGs during process vivo may evolutionarily advantageous through better evasion humoral responses directed against HCMV virions.