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 ؉ Tcell responses to UL111A deletion virusinfected myeloid progenitors, indicating that loss of the capacity to express IntroductionHuman cytomegalovirus (HCMV) is a species-specific -herpesvirus that infects a majority of the world's population. 1 During primary productive infection, both innate and adaptive immune responses are activated, and replicating virus is eventually cleared from the host. However, the virus is able to evade complete immune clearance by establishing and maintaining a life-long latent infection in hematopoietic cells, specifically those of the myeloid lineage. [2][3][4][5][6][7] During latency, detectable infectious virus production ceases, the viral genome is maintained as an extrachromosomal plasmid 8 at a low viral genome copy number, 7 and only a subset of viral genes remain transcriptionally active. [9][10][11][12][13][14] Reactivation from latency results in reinitiation of the full replicative cycle, with production of new infectious virus.Reactivation of HCMV from latency during states of reduced immune surveillance has profound implications for the management of patients with hematologic and immune deficiency disorders. In these clinical contexts, HCMV reactivation can lead to tissue infection causing major morbidity and mortality. As a result, the presence of HCMV seropositivity and thus of latent virus in donors or recipients of unrelated stem cell transplantations is an adverse prognostic feature despite major advances in HCMV monitoring and management. 15,16 Reactivation of HCMV is also of importance in seropositive patients with nontransplantation cellular immunodeficiencies, such as those resulting from human immunodeficiency virus infection, 17 or in seropositive patients with iatrogenically induced immunodeficiency, such as that resulting from treatment with the anti-CD52 antibody Campath. 18,19 There is no known therapy for the elimination of virus that persists during latency. Instead, where necessary, medical treatment has concentrated on the preemptive treatment or the prophylaxis of viral reactivation. Even here, no single strategy prevents reactivation while universally avoiding unnecessary therapy. There is an urge...
Human cytomegalovirus (HCMV), the largest human herpesvirus, infects a majority of the world’s population. Like all herpesviruses, following primary productive infection, HCMV establishes a life-long latent infection, from which it can reactivate years later to produce new, infectious virus. Despite the presence of a massive and sustained anti-HCMV immune response, productively infected individuals can shed virus for extended periods of time, and once latent infection is established, it is never cleared from the host. It has been proposed that HCMV must therefore encode functions which help to evade immune mediated clearance during productive virus replication and latency. Molecular mimicry is a strategy used by many viruses to subvert and regulate anti-viral immunity and HCMV has hijacked/developed a range of functions that imitate host encoded immunomodulatory proteins. This review will focus on the HCMV encoded homologs of cellular cytokines/chemokines and their receptors, with an emphasis on how these virus encoded homologs may facilitate viral evasion of immune clearance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.