scholarly journals Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of cGAS to Mediate Immune Evasion

2018 ◽  
Vol 24 (1) ◽  
pp. 69-80.e4 ◽  
Author(s):  
Zhe-Fu Huang ◽  
Hong-Mei Zou ◽  
Bo-Wei Liao ◽  
Hong-Yan Zhang ◽  
Yan Yang ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Dna Sensing

scholarly journals Evasion of Intracellular DNA Sensing by Human Herpesviruses

2021 ◽  
Vol 11 ◽  
Author(s):  
Debipreeta Bhowmik ◽  
Fanxiu Zhu
Keyword(s):  
Immune Evasion ◽  
Mammalian Cells ◽  
Adaptor Protein ◽  
Large Family ◽  
Immune Defense ◽  
Dna Sensor ◽  
Dna Sensing ◽  
Dna Viruses ◽  
Sensor Degradation ◽  
Human Herpesviruses

Sensing of viral constituents is the first and critical step in the host innate immune defense against viruses. In mammalian cells, there are a variety of pathogen recognition receptors (PRRs) that detect diverse pathogen-associated molecular patterns (PAMPs) including viral RNA and DNA. In the past decade, a number of host DNA sensors have been discovered and the underlying sensing mechanisms have been elucidated. Herpesviruses belong to a large family of enveloped DNA viruses. They are successful pathogens whose elaborate immune evasion mechanisms contribute to high prevalence of infection among their hosts. The three subfamilies of herpesviruses have all been found to employ diverse and overlapping strategies to interfere with host DNA sensing. These strategies include masking viral DNA or the DNA sensor, degradation of the DNA sensor, and post-transcriptional modification of the DNA sensor or its adaptor protein. In this review, we will discuss the current state of our knowledge on how human herpesviruses use these strategies to evade DNA-induced immune responses. Comprehensive understanding of herpesvirus immune-evasion mechanisms will aid in the development of vaccines and antivirals for herpesvirus-associated diseases.

scholarly journals Human Cytomegalovirus Inhibits Tapasin-Dependent Peptide Loading and Optimization of the MHC Class I Peptide Cargo for Immune Evasion

Immunity ◽  
2004 ◽  
Vol 20 (1) ◽  
pp. 71-85 ◽  
Author(s):  
Boyoun Park ◽  
Youngkyun Kim ◽  
Jinwook Shin ◽  
Sunray Lee ◽  
Kwangmin Cho ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Class I ◽  
Peptide Loading

Immune evasion by human cytomegalovirus: lessons in immunology and cell biology

2001 ◽  
Vol 13 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Wil A.M Loenen ◽  
C.A Bruggeman ◽  
E.J.H.J Wiertz
Keyword(s):  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Cell Biology

scholarly journals Human Cytomegalovirus miR-US33as-5p Targets IFNAR1 to Achieve Immune Evasion During Both Lytic and Latent Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Xin Song ◽  
Ping Ma ◽  
Liping Lv ◽  
Yangyang Zhang ◽  
...  
Keyword(s):  
Viral Load ◽  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Latent Infection ◽  
Signal Transduction Pathway ◽  
Luciferase Reporter ◽  
Type I ◽  
Immune Evasion Mechanism ◽  
Reporter Assays

As the first line of antiviral defense, type I interferon (IFN) binds IFN receptor 1 (IFNAR1) and IFNAR2 to activate the Jak-STAT signal transduction pathway, producing IFN-stimulated genes (ISGs) to control viral infection. The mechanisms by which human cytomegalovirus (HCMV) counteracts the IFN pathway are only partially defined. We show that miR-US33as-5p encoded by HCMV is expressed in both lytic and latent infection. By analysis with RNA hybrid and screening with luciferase reporter assays, we identified IFNAR1 as a target of hcmv-miR-US33as-5p, which was further verified by examining the expression of two IFNAR1 mutants and the binding of IFNAR1 to miR-US33as-5p/miR-US33as-5p-M1/miR-US33as-5p-M2. We found that after the transfection of miR-US33as-5p mimics into different cell lines, the phosphorylation of downstream proteins and ISG expression were downregulated. Immunofluorescence showed that the miR-US33as-5p mimics also inhibited STAT1 translocation into the nucleus. Furthermore, we constructed HCMV with mutant miR-US33as-5p and determined that the mutation did not affect HCMV replication. We found that MRC-5/human foreskin fibroblast (HFF) cells infected with ΔmiRNA HCMV exhibited higher IFNAR1 and ISG expression and a reduced viral load in the presence of exogenous IFN than cells infected with WT HCMV did, confirming that the knockout of miR-US33as-5p impaired viral resistance to IFN. Finally, we tested the effect of ΔmiRNA HCMV on THP-1 and d-THP-1 cells, common in vitro models of latent infection and reactivation, respectively. Again, we found that cells infected with ΔmiRNA HCMV showed a reduced viral load in the presence of IFN than the control cells did, confirming that miR-US33as-5p also affects IFN resistance during both latency and reactivation. These results indicate a new microRNA (miRNA)-based immune evasion mechanism employed by HCMV to achieve lifelong infection.

Diverse immune evasion strategies by human cytomegalovirus

2012 ◽  
Vol 54 (1-3) ◽  
pp. 140-151 ◽  
Author(s):  
Vanessa Noriega ◽  
Veronika Redmann ◽  
Thomas Gardner ◽  
Domenico Tortorella
Keyword(s):  
Human Cytomegalovirus ◽  
Immune Evasion

scholarly journals Tegument Proteins of Human Cytomegalovirus

2008 ◽  
Vol 72 (2) ◽  
pp. 249-265 ◽  
Author(s):  
Robert F. Kalejta
Keyword(s):  
Gene Expression ◽  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Viral Entry ◽  
Human Herpesvirus ◽  
Lytic Replication ◽  
Viral Envelope ◽  
Tegument Proteins ◽  
Composition And Structure ◽  
And Control

SUMMARY Human cytomegalovirus (HCMV) is a common, medically relevant human herpesvirus. The tegument layer of herpesvirus virions lies between the genome-containing capsids and the viral envelope. Proteins within the tegument layer of herpesviruses are released into the cell upon entry when the viral envelope fuses with the cell membrane. These proteins are fully formed and active and control viral entry, gene expression, and immune evasion. Most tegument proteins accumulate to high levels during later stages of infection, when they direct the assembly and egress of progeny virions. Thus, viral tegument proteins play critical roles at the very earliest and very last steps of the HCMV lytic replication cycle. This review summarizes HCMV tegument composition and structure as well as the known and speculated functions of viral tegument proteins. Important directions for future investigation and the challenges that lie ahead are identified and discussed.

scholarly journals Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

2016 ◽  
Vol 80 (3) ◽  
pp. 663-677 ◽  
Author(s):  
Thomas J. Gardner ◽  
Domenico Tortorella
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Humoral Immune Response ◽  
Cell Activation ◽  
Nk Cell ◽  
Cell Attachment ◽  
Immune Defense ◽  
Viral Glycoprotein ◽  
Humoral Immune

SUMMARYThe prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease.

scholarly journals Natural Killer Cells Can Inhibit the Transmission of Human Cytomegalovirus in Cell Culture by Using Mechanisms from Innate and Adaptive Immune Responses

2014 ◽  
Vol 89 (5) ◽  
pp. 2906-2917 ◽  
Author(s):  
Zeguang Wu ◽  
Christian Sinzger ◽  
Johanna Julia Reichel ◽  
Marlies Just ◽  
Thomas Mertens
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Hcmv Infection ◽  
Nk Cell ◽  
High Morbidity ◽  
Major Health Problem ◽  
Effector Cells ◽  
Infected Cells

ABSTRACTHuman cytomegalovirus (HCMV) transmission within the host is important for the pathogenesis of HCMV diseases. Natural killer (NK) cells are well known to provide a first line of host defense against virus infections. However, the role of NK cells in the control of HCMV transmission is still unknown. Here, we provide the first experimental evidence that NK cells can efficiently control HCMV transmission in different cell types. NK cells engage different mechanisms to control the HCMV transmission both via soluble factors and by cell contact. NK cell-produced interferon gamma (IFN-γ) suppresses HCMV production and induces resistance of bystander cells to HCMV infection. The UL16 viral gene contributes to an immune evasion from the NK cell-mediated control of HCMV transmission. Furthermore, the efficacy of the antibody-dependent NK cell-mediated control of HCMV transmission is dependent on a CD16-158V/F polymorphism. Our findings indicate that NK cells may have a clinical relevance in HCMV infection and highlight the need to consider potential therapeutic strategies based on the manipulation of NK cells.IMPORTANCEHuman cytomegalovirus (HCMV) infects 40% to 100% of the human population worldwide. After primary infection, mainly in childhood, the virus establishes a lifelong persistence with possible reactivations. Most infections remain asymptomatic; however, HCMV represents a major health problem since it is the most frequent cause of infection-induced birth defects and is responsible for high morbidity and mortality in immunocompromised patients. The immune system normally controls the infection by antibodies and immune effector cells. One type of effector cells are the natural killer (NK) cells, which provide a rapid response to virus-infected cells. NK cells participate in viral clearance by inducing the death of infected cells. NK cells also secrete antiviral cytokines as a consequence of the interaction with an infected cell. In this study, we investigated the mechanisms by which NK cells control HCMV transmission, from the perspectives of immune surveillance and immune evasion.

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