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Science 328 (5974): 102-106

Copyright © 2010 by the American Association for the Advancement of Science

Evasion of CD8+ T Cells Is Critical for Superinfection by Cytomegalovirus

Scott G. Hansen,1,* Colin J. Powers,1,*,{dagger} Rebecca Richards,1 Abigail B. Ventura,1 Julia C. Ford,1 Don Siess,2 Michael K. Axthelm,1,2 Jay A. Nelson,1,2 Michael A. Jarvis,1 Louis J. Picker,1,2,{ddagger} Klaus Früh1,2,{ddagger}

Abstract: Cytomegalovirus (CMV) can superinfect persistently infected hosts despite CMV-specific humoral and cellular immunity; however, how it does so remains undefined. We have demonstrated that superinfection of rhesus CMV–infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally encoded inhibitors of major histocompatibility complex class I (MHC-I) antigen presentation, particularly the homologs of human CMV US2, 3, 6, and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo, thus supporting viral replication and dissemination during superinfection, a process that complicates the development of preventive CMV vaccines but that can be exploited for CMV-based vector development.

1 Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.
2 Oregon National Primate Research Center, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.

* These authors contributed equally to this work.

{dagger} Present address: Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

{ddagger} To whom correspondence should be addressed. E-mail: pickerl{at}ohsu.edu (L.J.P.); fruehk{at}ohsu.edu (K.F.)

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