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Cell Host Microbe. 2011 Sep 15;10(3):197-209. doi: 10.1016/j.chom.2011.07.010.

Human cytomegalovirus escapes a naturally occurring neutralizing antibody by incorporating it into assembling virions.

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1
Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.

Abstract

Human cytomegalovirus (CMV) is a common but difficult to treat infection of immunocompromised patients. MSL-109 is a human monoclonal IgG isolated from a CMV seropositive individual that recognizes the viral glycoprotein H (gH) surface antigen complexes that mediate entry. Although MSL-109 blocks CMV infection in vitro, it lacked sufficient efficacy in human trials, and CMV isolated from treated patients suggested the evolution of MSL-109 resistance. To understand how CMV escapes MSL-109, we characterized a MSL-109-resistant CMV strain. Our results elucidate a nongenetic escape mechanism in which the antibody is selectively taken up by infected cells and incorporated into assembling virions in a dose-dependent manner. The resistant virus then utilizes the Fc domain of the incorporated antibody to infect naive nonimmune cells. This resistance mechanism may explain the clinical failure of MSL-109, illustrate a general mechanism of viral antibody escape, and inform antiviral vaccine and therapeutic development.

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PMID:
21925108
DOI:
10.1016/j.chom.2011.07.010
[Indexed for MEDLINE]
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