The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency.
The capacity of human cytomegalovirus (HCMV) to establish and maintain a latent infection from which it can later reactivate ensures its widespread distribution in the population, but the mechanisms enabling maintenance of latency in the face of a robust immune system are poorly understood. We examined the role of the HCMV UL111A gene, which encodes homologs of the immunosuppressive cytokine interleukin-10 in the context of latent infection of myeloid progenitor cells. A UL111A deletion virus was able to establish, maintain, and reactivate from experimental latency in a manner comparable with parental virus, but major histocompatibility complex class II levels increased significantly on the surfaces of cells infected with the deletion virus. Importantly, there was an increase in both allogeneic and autologous peripheral blood mononuclear cells and CD4(+) T-cell responses to UL111A deletion virus-infected myeloid progenitors, indicating that loss of the capacity to express viral interleukin-10 during latency results in latently infected cells becoming more readily recognizable by a critical arm of the immune response. The detection of a viral gene that suppresses CD4(+) T-cell recognition of latently infected cells identifies an immune evasion strategy that probably enhances the capacity of HCMV to persist in a latent state within the human host.
Cheung
Allen K L
AK
Centre for Virus Research, Westmead Millennium Institute and University of Sydney, Westmead, NSW 2145, Australia.
Gottlieb
David J
DJ
Plachter
Bodo
B
Pepperl-Klindworth
Sandra
S
Avdic
Selmir
S
Cunningham
Anthony L
AL
Abendroth
Allison
A
Slobedman
Barry
B
D001324:Autoantigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D015536:Down-Regulation; D017353:Gene Deletion; D005814:Genes, Viral; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007519:Isoantigens; D023461:Myeloid Progenitor Cells / Q000276:immunology / Q000821:virology; D017735:Virus Latency / Q000276:immunology*
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens