Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency.
Jared E. Knickelbein,Kamal M. Khanna,Michael B. Yee,Catherine J. Baty,Paul R. Kinchington,Robert L. Hendricks +5 more
TLDR
It is found that CD8+ T cell lytic granules are also required for the maintenance of neuronal latency both in vivo and in ex vivo ganglia cultures and that their directed release to the junction with neurons in latently infected ganglia did not induce neuronal apoptosis.Abstract:
Reactivation of herpes simplex virus type 1 (HSV-1) from neuronal latency is a common and potentially devastating cause of disease worldwide. CD8+ T cells can completely inhibit HSV reactivation in mice, with interferon-gamma affording a portion of this protection. We found that CD8+ T cell lytic granules are also required for the maintenance of neuronal latency both in vivo and in ex vivo ganglia cultures and that their directed release to the junction with neurons in latently infected ganglia did not induce neuronal apoptosis. Here, we describe a nonlethal mechanism of viral inactivation in which the lytic granule component, granzyme B, degrades the HSV-1 immediate early protein, ICP4, which is essential for further viral gene expression.read more
Citations
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Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus
Thomas Gebhardt,Linda M. Wakim,Liv Eidsmo,Patrick C. Reading,William R. Heath,Francis R. Carbone +5 more
TL;DR: A unique memory T cell subset present after acute infection with herpes simplex virus that remained resident in the skin and in latently infected sensory ganglia is described, representing an example of tissue-resident memory T cells that can provide protective immunity at points of pathogen entry.
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Redefining Chronic Viral Infection
TL;DR: Changing concepts of etiologies for diseases, especially those with a chronic inflammatory component, as well as how the authors design and interpret genome-wide association studies, and how they vaccinate to limit or control their virome, are required.
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Tissue-Resident Memory T Cells
Jason M. Schenkel,David Masopust +1 more
TL;DR: This review will summarize current knowledge of Trm cell ontogeny, regulation, maintenance, and function and will highlight technical considerations for studying this population.
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Tissue-resident memory T cells
Haina Shin,Akiko Iwasaki +1 more
TL;DR: Different tissues in the body are categorized based on patterns of memory T‐cell migration and tissue residency, which describes the rules for TRM generation and the properties that distinguish them from circulating TEM and TCM cells.
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Immune surveillance in the central nervous system.
Shalina S. Ousman,Paul Kubes +1 more
TL;DR: The physiological roles of the immune sentinels that patrol the CNS, the molecular markers that underlie their surveillance duties, and the consequences of interrupting their functions following injury and infection by viruses such as JC virus, human immunodeficiency virus, herpes simplex virus and West Nile virus are discussed.
References
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Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4.
TL;DR: Immediate-early polypeptides ICP0 and ICP27 were expressed to a higher level in Vero cells infected with an ICP4 temperature-sensitive (ts) mutant (tsB32) at 39 degrees C, indicating immediate-early stimulatory activity associated with the ts I CP4 polypePTide.
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MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs
Jennifer L. Umbach,Martha F. Kramer,Igor Jurak,Heather W. Karnowski,Donald M. Coen,Bryan R. Cullen +5 more
TL;DR: HSV-1 expresses at least two primary miRNA precursors in latently infected neurons that may facilitate the establishment and maintenance of viral latency by post-transcriptionally regulating viral gene expression.
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Virus-Induced Neuronal Apoptosis Blocked by the Herpes Simplex Virus Latency-Associated Transcript
Guey Chuen Perng,Clinton Jones,Janice R. Ciacci-Zanella,Melissa Stone,Gail A. Henderson,Ada Yukht,Susan M. Slanina,Florence M. Hofman,Homayon Ghiasi,Homayon Ghiasi,Anthony B. Nesburn,Anthony B. Nesburn,Steven L. Wechsler,Steven L. Wechsler +13 more
TL;DR: In rabbit trigeminal ganglia, extensive apoptosis occurred with LAT(-) virus but not with LAT (+) viruses, and a plasmid expressing LAT blocked apoptosis in cultured cells, suggesting that LAT promotes neuronal survival after HSV-1 infection by reducing apoptosis.
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Cd8+ T Cells Can Block Herpes Simplex Virus Type 1 (HSV-1) Reactivation from Latency in Sensory Neurons
TL;DR: It is demonstrated 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, and it is proposed 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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Chromatin control of herpes simplex virus lytic and latent infection
David M. Knipe,Anna R. Cliffe +1 more
TL;DR: A model for the decision to undergo a lytic or a latent infection in which HSV encodes gene products that modulate chromatin structure towards either euchromatin or heterochromatin is proposed and the implications for the development of therapeutics for HSV infections are discussed.