scholarly journals Elimination of HSV-2 infected cells is mediated predominantly by paracrine effects of tissue-resident T cell derived cytokines

2019 ◽  
Author(s):  
Pavitra Roychoudhury ◽  
David A Swan ◽  
Elizabeth Duke ◽  
Lawrence Corey ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Lesion Size ◽  
Viral Kinetics ◽  
Paracrine Effects ◽  
Alarm Signaling ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

AbstractThe mechanisms underlying rapid elimination of herpes simplex virus-2 (HSV-2) in the human genital tract despite low tissue-resident CD8+ T-cell density (TRM) are unknown. We analyzed shedding episodes during chronic HSV-2 infection: viral clearance always occurred within 24 hours of detection even if viral load exceeded 107HSV DNA copies; surges in granzyme B and interferon-γoccurred within the early hours after reactivation. We next developed a mathematical model of an HSV-2 genital ulcer to integrate mechanistic observations of TRMin situproliferation, trafficking, cytolytic effects and cytokine alarm signaling from murine studies with viral kinetics, histopathology and lesion size data from humans. A sufficiently high density of HSV-2 specific TRMpredicted rapid contact-mediated elimination of infected cells. At lower TRMdensities, TRMmust initiate a rapidly diffusing, polyfunctional cytokine response in order to eliminate of a majority of infected cells and eradicate briskly spreading HSV-2 infection.One Sentence SummaryControl of herpes simplex virus-2 is primarily mediated by rapidly diffusing cytokines secreted by tissue-resident T cells.

scholarly journals Tissue-resident T cell–derived cytokines eliminate herpes simplex virus-2–infected cells

2020 ◽  
Vol 130 (6) ◽  
pp. 2903-2919 ◽  
Author(s):  
Pavitra Roychoudhury ◽  
David A. Swan ◽  
Elizabeth Duke ◽  
Lawrence Corey ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

scholarly journals Impact of asymptomatic Herpes simplex virus-2 infection on T cell phenotype and function in the foreskin

AIDS ◽  
2012 ◽  
Vol 26 (10) ◽  
pp. 1319-1322 ◽  
Author(s):  
Jessica L. Prodger ◽  
Ronald Gray ◽  
Godfrey Kigozi ◽  
Fred Nalugoda ◽  
Ronald Galiwango ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Cell Phenotype ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
And Function

scholarly journals Short Communication: T Cell Activation in HIV-1/Herpes Simplex Virus-2-Coinfected Kenyan Women Receiving Valacyclovir

2013 ◽  
Vol 29 (1) ◽  
pp. 94-98 ◽  
Author(s):  
Alison C. Roxby ◽  
Amy Y. Liu ◽  
Alison L. Drake ◽  
James N. Kiarie ◽  
Barbra Richardson ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Short Communication ◽  
Kenyan Women ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Hiv 1

scholarly journals Herpes Simplex Virus 2 UL45 Is a Type II Membrane Protein

1998 ◽  
Vol 72 (5) ◽  
pp. 4430-4433 ◽  
Author(s):  
Adam S. Cockrell ◽  
Martin I. Muggeridge
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Membrane Protein ◽  
Integral Membrane Protein ◽  
Type Ii ◽  
Glycosylation Sites ◽  
Infected Cells ◽  
Membrane Spanning ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACT In addition to eleven glycoproteins, the herpes simplex virus type 2 (HSV-2) genome encodes several proteins with potential membrane-spanning segments but no asparagine-linked carbohydrates. One of these is UL45. Fractionation of infected cells showed that HSV-2 UL45 is an integral membrane protein, and analysis of UL45 mutants with potential glycosylation sites showed that it has a type II membrane orientation, the first HSV protein known to have this orientation. Furthermore, it is detectable in infected cells at a time similar to that when glycoproteins gB and gD are detected, consistent with a role in cell-cell fusion, which has previously been found for HSV-1 UL45.

scholarly journals Thin-layer immunoassay for determination of antibodies to herpes simplex virus

1979 ◽  
Vol 9 (3) ◽  
pp. 317-322
Author(s):  
S Jeansson ◽  
H Elwing ◽  
L A Nilsson
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thin Layer ◽  
False Negative ◽  
Virus Antigen ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

Thin-layer immunoassay (TIA) is a simple serological technique suitable for analysis of large numbers of samples. In this study, TIA was evaluated for determination of antibodies to herpes simplex virus. Herpes simplex virus antigen used in TIA was purified from material released from virus-infected cells. The results obtained by TIA were compared with those obtained by neutralization and complement fixation tests. TIA was found to be as sensitive as the neutralization test for demonstration of herpes simplex virus antibodies. No false-negative or -positive reactions were observed. In primary herpes simplex virus-1 infections, an antibody response was demonstrated by TIA, whereas antibodies could not be demonstrated in patients with primary herpes simplex virus-2 infections.

scholarly journals Antiviral Activity of a Single-Domain Antibody Immunotoxin Binding to Glycoprotein D of Herpes Simplex Virus 2

2014 ◽  
Vol 59 (1) ◽  
pp. 527-535 ◽  
Author(s):  
Eileen M. Geoghegan ◽  
Hong Zhang ◽  
Prashant J. Desai ◽  
Arya Biragyn ◽  
Richard B. Markham
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Single Domain ◽  
Surface Glycoprotein ◽  
Glycoprotein D ◽  
Single Domain Antibody ◽  
Domain Antibody ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACTDespite years of research dedicated to preventing the sexual transmission of herpes simplex virus 2 (HSV-2), there is still no protective vaccine or microbicide against one of the most common sexually transmitted infections in the world. Using a phage display library constructed from a llama immunized with recombinant HSV-2 glycoprotein D, we identified a single-domain antibody VHH, R33, which binds to the viral surface glycoprotein D. Although R33 does not demonstrate any HSV-2 neutralization activityin vitro, when expressed with the cytotoxic domain of exotoxin A, the resulting immunotoxin (R33ExoA) specifically and potently kills HSV-2-infected cells, with a 50% neutralizing dilution (IC50) of 6.7 nM. We propose that R33ExoA could be used clinically to prevent transmission of HSV-2 through killing of virus-producing epithelial cells during virus reactivation. R33 could also potentially be used to deliver other cytotoxic effectors to HSV-2-infected cells.

scholarly journals Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Joshua T Schiffer ◽  
David Swan ◽  
Ramzi Al Sallaq ◽  
Amalia Magaret ◽  
Christine Johnston ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Genital Tract ◽  
Time Intervals ◽  
Host Immune Responses ◽  
Spatial Propagation ◽  
Infected Cells ◽  
Episode Duration ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium.

Sign in / Sign up

Export Citation Format

Share Document