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Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

Nature Medicine volume 19, pages 280–288 (2013)Cite this article

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Abstract

Herpes simplex virus-2 (HSV-2) is periodically shed throughout the human genital tract. Although a high viral load correlates with the development of genital ulcers, shedding also commonly occurs even when ulcers are absent, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs within ganglia despite diverse and complementary host and viral mechanisms that predispose toward latency, suggesting that viral replication may be constantly occurring in a small minority of neurons at these sites. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-2 specific T cells persist at prior sites of genital tract reactivation and, in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. The fact that immune responses usually control viral replication in genital skin before lesions develop provides hope that enhancing such responses could lead to effective vaccines and immunotherapies.

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Figure 1: Prevalence of HSV-2 infection in women.
Figure 2: Schematic and histologic representation of healthy genital mucosa.
Figure 3: HSV-2 reactivation dynamics.
Figure 4: HSV-2 and host interactions in nerve root ganglia.
Figure 5: Host immunity in the genital mucosa.

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Acknowledgements

We are grateful to M. Miner for her contribution in the editorial preparation of the manuscript and to our reviewers for their insightful suggestions. This work was supported by US National Institutes of Health grants P01 AI030731, R37 AI042528 and K23 AI087206.

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Authors and Affiliations

  1. Department of Medicine, University of Washington, Seattle, Washington, USA

    Joshua T Schiffer & Lawrence Corey

  2. Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Joshua T Schiffer & Lawrence Corey

  3. Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA

    Lawrence Corey

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  1. Joshua T Schiffer
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Correspondence to Joshua T Schiffer.

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Competing interests

L.C. is a member of the scientific advisory board and a founder of Immune Design Corporation, which is considering development of an immunotherapeutic HSV-2 vaccine.

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Schiffer, J., Corey, L. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection. Nat Med 19, 280–288 (2013). https://doi.org/10.1038/nm.3103

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