Pathogenesis and virulence of herpes simplex virus

Virulence. 2021 Dec;12(1):2670-2702. doi: 10.1080/21505594.2021.1982373.


Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. The intrinsic, innate and adaptive immune responses are key to control HSV, and the virus has developed mechanisms to evade them. The immune response can also contribute to pathogenesis, as observed in stromal keratitis and encephalitis. The fact that certain individuals are more prone than others to suffer severe disease upon HSV infection can be partially explained by the existence of genetic polymorphisms in humans. Like all herpesviruses, HSV has two replication cycles: lytic and latent. During lytic replication HSV produces infectious viral particles to infect other cells and organisms, while during latency there is limited gene expression and lack of infectious virus particles. HSV establishes latency in neurons and can cause disease both during primary infection and upon reactivation. The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. Here we review the HSV life cycle, the interaction of HSV with the immune system and three of the best-studied pathologies: Herpes stromal keratitis, herpes simplex encephalitis and genital herpes. We also discuss the potential association between HSV-1 infection and Alzheimer's disease.

Keywords: Herpes simplex virus; genital herpes; herpes and Alzheimer’s disease; herpes simplex encephalitis; herpes stromal keratitis; pathogenesis; virulence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Encephalitis*
  • Female
  • Herpes Genitalis*
  • Herpes Simplex* / pathology
  • Herpesvirus 1, Human* / genetics
  • Humans
  • Male
  • Virulence
  • Virus Latency / physiology

Grants and funding

This work was funded by the Deutsche Forschungsgemeinschaft (DFG [German Research Foundation]) under Germany’s Excellence Strategy - EXC 2155 “RESIST” - project number 39087428.