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Hijacking an antibody

Nature Medicine volume 17, page 1199 (2011) | Download Citation

Genetic mutations often drive viral escape from antibody-mediated neutralization. A new study describes an alternative form of resistance where human cytomegalovirus (CMV) incorporates the antibody and uses it to subsequently infect new cells.

The human monoclonal IgG MSL-192 recognizes the viral glycoprotein H (gH) and blocks infection of fibroblasts with CMV in vitro. Clinical trials with MSL-109 were halted due to insufficient efficacy in treating patients with AIDS and CMV-induced retinitis.

Kate Manley et al. (Cell Host Microbe 10, 197–209) found that, following multiple rounds of infection in vitro, an MSL-109–resistant CMV strain emerged. This resistance was reversible and was not associated with genetic changes. Instead, the antibody was taken up by CMV-infected cells. Once inside the cell, it interacts with gH and is incorporated into assembling virions during their maturation. The Fc domain of the incorporated MSL-109 is then used by CMV to infect nonimmune cells. Although the precise details of viral entry remain unclear, these findings provide insight into a previously undescribed mechanism of viral escape.

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