scholarly journals Us3 Kinase Encoded by Herpes Simplex Virus 1 Mediates Downregulation of Cell Surface Major Histocompatibility Complex Class I and Evasion of CD8+ T Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72050 ◽  
Author(s):  
Takahiko Imai ◽  
Naoto Koyanagi ◽  
Ryo Ogawa ◽  
Keiko Shindo ◽  
Tadahiro Suenaga ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Complex Class ◽  
Herpes Simplex Virus 1 ◽  
Histocompatibility Complex ◽  
Simplex Virus

scholarly journals Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons.

1992 ◽  
Vol 175 (5) ◽  
pp. 1337-1344 ◽  
Author(s):  
A Simmons ◽  
D C Tscharke
Keyword(s):  
T Cells ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd8 T Cells ◽  
Genetic Determinants ◽  
Histocompatibility Complex ◽  
Sensory Nervous System ◽  
Simplex Virus

The role of CD8+ T cells in resistance to herpes simplex virus (HSV) was examined. After cutaneous inoculation, HSV spreads to the peripheral nervous system (PNS) where it replicates in ganglionic neurons. In normal mice, replication of virus in the PNS was rapidly terminated and evidence of neuronal destruction, assessed by a quantitative histological assay, was sparse. Clearance of infectious virus was impaired, and a strikingly high proportion of ganglionic neurons was killed, in mice treated with an antibody that depleted them of CD8+ T cells. These results suggest that CD8+ T cells play an important role in maintaining the integrity of the sensory nervous system during primary infection with HSV. Therefore, viral epitopes recognized by CD8+ T cells and restricting class I major histocompatibility complex genes are, in principle, implicated as interacting genetic determinants of neurovirulence.

scholarly journals Selective Expression of CCR10 and CXCR3 by Circulating Human Herpes Simplex Virus-Specific CD8 T Cells

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Michael T. Hensel ◽  
Tao Peng ◽  
Anqi Cheng ◽  
Stephen C. De Rosa ◽  
Anna Wald ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Chemokine Receptors ◽  
Mrna Levels ◽  
Skin Homing ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) infection is restricted to epithelial cells and neurons and is controlled by CD8 T cells. These cells both traffic to epithelial sites of recurrent lytic infection and to ganglia and persist at the dermal-epidermal junction for up to 12 weeks after lesion resolution. We previously showed that cutaneous lymphocyte-associated antigen (CLA), a functional E-selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8 T cells. CLA/ESL mediates adhesion of T cells to inflamed vascular endothelium. Later stages in T-cell homing involve chemokines (Ch) and lymphocyte chemokine receptors (ChR) for vascular wall arrest and diapedesis. Several candidate ChR have been implicated in skin homing. We measured cell surface ChR on HSV-specific human peripheral blood CD8 T cells and extended our studies to HSV-1. We observed preferential cell surface expression of CCR10 and CXCR3 by HSV-specific CD8 T cells compared to CD8 T cells specific for control viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), and compared to bulk memory CD8 T cells. CXCR3 ligand mRNA levels were selectively increased in skin biopsy specimens from persons with recurrent HSV-2, while the mRNA levels of the CCR10 ligand CCL27 were equivalent in lesion and control skin. Our data are consistent with a model in which CCL27 drives baseline recruitment of HSV-specific CD8 T cells expressing CCR10, while interferon-responsive CXCR3 ligands recruit additional cells in response to virus-driven inflammation. IMPORTANCE HSV-2 causes very localized recurrent infections in the skin and genital mucosa. Virus-specific CD8 T cells home to the site of recurrent infection and participate in viral clearance. The exit of T cells from the blood involves the use of chemokine receptors on the T-cell surface and chemokines that are present in infected tissue. In this study, circulating HSV-2-specific CD8 T cells were identified using specific fluorescent tetramer reagents, and their expression of several candidate skin-homing-associated chemokine receptors was measured using flow cytometry. We found that two chemokine receptors, CXCR3 and CCR10, are upregulated on HSV-specific CD8 T cells in blood. The chemokines corresponding to these receptors are also expressed in infected tissues. Vaccine strategies to prime CD8 T cells to home to HSV lesions should elicit these chemokine receptors if possible to increase the homing of vaccine-primed cells to sites of infection.

scholarly journals A tumor escape variant that has lost one major histocompatibility complex class I restriction element induces specific CD8+ T cells to an antigen that no longer serves as a target.

1993 ◽  
Vol 178 (3) ◽  
pp. 933-940 ◽  
Author(s):  
S Seung ◽  
J L Urban ◽  
H Schreiber
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Major Histocompatibility Complex Class ◽  
Cd8 T Cells ◽  
Complex Class ◽  
Ctl Response ◽  
Escape Variant ◽  
Histocompatibility Complex

After loss of expression of a major histocompatibility complex class I Kk allele, the escape variant of an immunogenic tumor grows progressively in normal mice. This progressor variant is resistant to killing by cytotoxic T lymphocytes (CTLs) directed against the A and B antigens presented by Kk. Although the variant retains the expression of the Dk allele and is sensitive to CTLs directed against the C antigen presented by Dk, the variant failed to induce CTLs to this antigen in vivo. Instead, the variant induced CD8+ T cells directed to the A antigen. This was shown at the molecular level by T cell receptor beta chain sequence analysis of the responding cells. Further evidence for the presence of A antigen in the variant came from the finding that spleen cells of mice injected intraperitoneally with the variant tumor cells were primed for an anti-A CD8+ CTL response in vivo. Thus, in contrast to other variants that lost a target antigen and induced a CTL response to remaining target antigens, the Kk loss variant continued to induce an immune response to a tumor antigen that is no longer presented on the tumor cell surface. Even though the variant escapes in a single step because an effective CTL response to secondary antigens is prevented, these secondary antigens remain as potential targets of immunotherapy on the variant's cell surface.

scholarly journals An Important Role for Major Histocompatibility Complex Class I-Restricted T Cells, and a Limited Role for Gamma Interferon, in Protection of Mice against Lethal Herpes Simplex Virus Infection

1999 ◽  
Vol 73 (3) ◽  
pp. 2058-2063 ◽  
Author(s):  
Ai-Xuan Holterman ◽  
Kathleen Rogers ◽  
Kurt Edelmann ◽  
David M. Koelle ◽  
Lawrence Corey ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mhc Class I ◽  
Gamma Interferon ◽  
Class I ◽  
Histocompatibility Complex ◽  
Ifn Γ ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) inhibits major histocompatibility complex (MHC) class I expression in infected cells and does so much more efficiently in human cells than in murine cells. Given this difference, if MHC class I-restricted T cells do not play an important role in protection of mice from HSV, an important role for these cells in humans would be unlikely. However, the contribution of MHC class I-restricted T cells to the control of HSV infection in mice remains unclear. Further, the mechanisms by which these cells may act to control infection, particularly in the nervous system, are not well understood, though a role for gamma interferon (IFN-γ) has been proposed. To address the roles of MHC class I and of IFN-γ, C57BL/6 mice deficient in MHC class I expression (β2 microglobulin knockout [β2KO] mice), in IFN-γ expression (IFN-γKO mice), or in both (IFN-γKO/β2KO mice) were infected with HSV by footpad inoculation. β2KO mice were markedly compromised in their ability to control infection, as indicated by increased lethality and higher concentrations of virus in the feet and spinal ganglia. In contrast, IFN-γ appeared to play at most a limited role in viral clearance. The results suggest that MHC class I-restricted T cells play an important role in protection of mice against neuroinvasive HSV infection and do so largely by mechanisms other than the production of IFN-γ.

scholarly journals Cbl E3 Ligase Mediates the Removal of Nectin-1 from the Surface of Herpes Simplex Virus 1-Infected Cells

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Thibaut Deschamps ◽  
Christos Dogrammatzis ◽  
Ranajoy Mullick ◽  
Maria Kalamvoki
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Growth Factor ◽  
Cell Surface ◽  
E3 Ligase ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus ◽  
Entry Receptor ◽  
Hsv 1

ABSTRACT The Cbl E3 ligase has been linked to the down-modulation of surface signaling responses by inducing internalization of surface receptors. The adaptor protein CIN85 is a partner of Cbl that augments many of these interactions. Previously, an interaction was demonstrated between ICP0 and CIN85, which results in the removal of epidermal growth factor receptor (EGFR) from the surface of the infected cells with a concomitant attenuation of EGFR signaling. Here, we examined whether Cbl mediates the removal of the herpes simplex virus 1 (HSV-1) entry receptor Nectin-1 from the surface of infected cells. We found the following: (i) that Cbl, Nectin-1, and the viral glycoprotein D (gD) form a complex in infected cells; (ii) that during infection Nectin-1 is removed from the surface of the infected cells but is retained on the surface of cells that have been depleted of Cbl; and (iii) that in cells infected with a ΔICP0 mutant virus, Nectin-1 remained on the cell surface. Thus, Cbl is necessary but not sufficient for the removal of Nectin-1 from the cell surface. In addition, we observed that in Cbl-depleted cells there was enhanced entry after infection. These cells were susceptible to secondary infections by HSV-1. Viral entry in CIN85-depleted cells was only moderately enhanced compared to that in the Cbl-depleted cells, suggesting that the Cbl–Nectin-1 interaction is likely the key to the downregulation of surface Nectin-1. The removal of the HSV-1 entry receptor Nectin-1 from the surface of the infected cells may be part of the strategy of the virus to efficiently spread to uninfected cells. IMPORTANCE The Cbl E3 ligase suppresses surface signaling responses by inducing internalization of surface components. The targets of Cbl include such components as immune system receptors, growth factor receptors, adhesion, and cell-to-cell contact molecules. The immediate early protein ICP0 of herpes simplex virus 1 (HSV-1) interacts with CIN85, an adaptor protein that augments Cbl functions. The consequence of this interaction is the removal of the epidermal growth factor receptor (EGFR) from the surface of the infected cells with concomitant suppression of the EGF ligand signaling. The viral entry receptor Nectin-1 is also internalized during HSV-1 infection in a Cbl-dependent mechanism, and that increases the opportunity of the virus to spread to uninfected cells. The diversion of the Cbl/CIN85 endocytic machinery may be a strategy utilized by the virus to alter the cell surface pattern to prevent detrimental host responses.

scholarly journals Cd8+ T Cells Can Block Herpes Simplex Virus Type 1 (HSV-1) Reactivation from Latency in Sensory Neurons

2000 ◽  
Vol 191 (9) ◽  
pp. 1459-1466 ◽  
Author(s):  
Ting Liu ◽  
Kamal M. Khanna ◽  
XiaoPing Chen ◽  
David J. Fink ◽  
Robert L. Hendricks
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sensory Neurons ◽  
Cd8 T Cells ◽  
Early Proteins ◽  
Latently Infected ◽  
Simplex Virus ◽  
Hsv 1

Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8+ T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8+ T cells that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infected neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8α monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8+ T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8+ T cells aborting virion production.

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