Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 21;14(5):862.
doi: 10.3390/v14050862.

Fraternal Twins: The Enigmatic Role of the Immune System in Alphaherpesvirus Pathogenesis and Latency and Its Impacts on Vaccine Efficacy

Barry T Rouse  1 , D Scott Schmid  2
Affiliations
Review

Fraternal Twins: The Enigmatic Role of the Immune System in Alphaherpesvirus Pathogenesis and Latency and Its Impacts on Vaccine Efficacy

Barry T Rouse et al. Viruses. .

Abstract

Although the establishment, maintenance and reactivation from alphaherpesvirus latency is far from fully understood, some things are now manifestly clear: Alphaherpesvirus latency occurs in neurons of the peripheral nervous system and control of the process is multifactorial and complex. This includes components of the immune system, contributions from non-neuronal cells surrounding neurons in ganglia, specialized nucleic acids and modifications to the viral DNA to name some of the most important. Efficacious vaccines have been developed to control both acute varicella and zoster, the outcome of reactivation, but despite considerable effort vaccines for acute herpes simplex virus (HSV) infection or reactivated lesions have thus far failed to materialize despite considerable effort. Given the relevance of the immune system to establish and maintain HSV latency, a vaccine designed to tailor the HSV response to maximize the activity of components most critical for controlling reactivated infection might limit the severity of recurrences and hence reduce viral transmission. In this review, we discuss the current understanding of immunological factors that contribute to HSV and VZV latency, identify differences between varicella-zoster virus (VZV) and HSV that could explain why vaccines have been valuable at controlling VZV disease but not HSV, and finish by outlining possible strategies for developing effective HSV vaccines.

Keywords: anti-herpesvirus vaccines; herpes simplex virus; immunity; latency; varicella zoster virus.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bloom D.C. Alphaherpesvirus Latency: A Dynamic State of Transcription and Reactivation. Adv. Virus Res. 2016;94:53–80. doi: 10.1016/bs.aivir.2015.10.001. - DOI - PubMed
    1. Roizman B., Whitley R.J. An Inquiry into the Molecular Basis of HSV Latency and Reactivation. Ann. Rev. Microbiol. 2013;67:355–374. doi: 10.1146/annurev-micro-092412-155654. - DOI - PubMed
    1. Cohen J.I. Herpesvirus latency. J. Clin. Investig. 2020;130:3361–3369. doi: 10.1172/JCI136225. - DOI - PMC - PubMed
    1. Jones C. Reactivation from latency by alpha-herpesvirinae submfamily members: A stressful stimulation. Curr. Top. Virol. 2014;12:99–118.
    1. Azarkh Y., Gilden D., Cohrs R.J. Molecular characterization of varicella zoster virus in latently infected human ganglia: Physical state and abundance of VZV DNA, quantitation of viral transcripts and detection of VZV-specific proteins. Curr. Top. Microbiol. Immunol. 2010;342:229–241. doi: 10.1007/82_2009_2. - DOI - PMC - PubMed

Publication types