Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus.
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.
Hansen
Scott G
SG
Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.
Powers
Colin J
CJ
Richards
Rebecca
R
Ventura
Abigail B
AB
Ford
Julia C
JC
Siess
Don
D
Axthelm
Michael K
MK
Nelson
Jay A
JA
Jarvis
Michael A
MA
Picker
Louis J
LJ
Früh
Klaus
K
D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology*; D022482:Cytomegalovirus Vaccines / Q000276:immunology; D004195:Disease Models, Animal; D015683:Gene Products, gag / Q000276:immunology; D005814:Genes, Viral; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D057131:Immune Evasion; D007155:Immunologic Factors / Q000235:genetics / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D015163:Superinfection; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication; D017201:Virus Shedding
D022482:Cytomegalovirus Vaccines; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors; D014764:Viral Proteins