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Review

The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection

1
Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW 2145, Australia
2
Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia
3
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616, USA
4
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2000, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Maria Kalamvoki
Viruses 2021, 13(3), 359; https://doi.org/10.3390/v13030359
Received: 30 December 2020 / Revised: 5 February 2021 / Accepted: 22 February 2021 / Published: 25 February 2021
(This article belongs to the Special Issue Pathogenesis and Novel Antiviral Targets of Alphaherpesviruses)
Tissue-resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8+ TRM, there has recently been increased interest in defining the phenotype and the role of CD4+ TRM in diseases. Circulating CD4+ T cells seed CD4+ TRM, but there also appears to be an equilibrium between CD4+ TRM and blood CD4+ T cells. CD4+ TRM are more mobile than CD8+ TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8+ TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4+ and CD8+ TRM persisting between lesions may control asymptomatic shedding through interferon-gamma secretion, although this has been more clearly shown for CD8+ T cells. The exact role of the CD4+/CD8+ TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4+ TRM have now been shown to be a major target for productive and latent infection in the cervix. In HSV and HIV co-infections, CD4+ TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4+ TRM and their induction by vaccines may help control sexual transmission by both viruses. View Full-Text
Keywords: HIV-1; HSV-1/2; tissue resident CD4+; CD8+; vaccines; infection; immunity; keratitis HIV-1; HSV-1/2; tissue resident CD4+; CD8+; vaccines; infection; immunity; keratitis
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MDPI and ACS Style

O’Neil, T.R.; Hu, K.; Truong, N.R.; Arshad, S.; Shacklett, B.L.; Cunningham, A.L.; Nasr, N. The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection. Viruses 2021, 13, 359. https://doi.org/10.3390/v13030359

AMA Style

O’Neil TR, Hu K, Truong NR, Arshad S, Shacklett BL, Cunningham AL, Nasr N. The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection. Viruses. 2021; 13(3):359. https://doi.org/10.3390/v13030359

Chicago/Turabian Style

O’Neil, Thomas R., Kevin Hu, Naomi R. Truong, Sana Arshad, Barbara L. Shacklett, Anthony L. Cunningham, and Najla Nasr. 2021. "The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection" Viruses 13, no. 3: 359. https://doi.org/10.3390/v13030359

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