Herpes simplex virus

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as human herpesvirus 1 and 2 (HHV-1 and HHV-2), are two members of the eight known members of the herpesviridae family. Both are lifelong infections and mostly asymptomatic.

Overview
HSV-1 is mainly transmitted by oral contact and causes cold sores, but can also cause genital herpes (persons with oral HSV-1 are unlikely to subsequently contract genital HSV-1.) HSV-1 is a highly common virus, found in an estimated 67% of the worldwide population under the age of 50. HSV-1 is most contagious while symptomatic, but can also be transmitted while asymptomatic.

HSV-2 is sexually transmitted and causes most cases of genital herpes. HSV-2 infection increases the risk of contracting and transmitting HIV. In the age group of 15 to 49, an estimated 11% of the global population has HSV-2.

Treatment
Standard treatment for herpes simplex virus include acyclovir, famciclovir, and valacyclovir. These medications can reduce frequency and severity of symptoms (but do not cure the infection).

Basic research
An in vitro study found HSV-1 (as well as the influenza virus) inhibited the mitochondrial respiratory chain. In the case of HSV-1, it reduced cellular respiration by targeting a site between complexes II and III, mediated by protein US3, and reduced the oxygen consumption rate by 31%.

Implication in other diseases
Dr. William Pridgen hypothesizes that fibromyalgia may be caused by HSV-1 infection in the dorsal root ganglia of the spine (and/or in other nerve ganglia), and treats fibromyalgia with an antiviral combination drug, called IMC-1, comprised of famciclovir (Famvir) and the COX-2 inhibitor drug celecoxib. A randomized, double-blinded, placebo-controlled study clinical trial of 143 fibromyalgia patients by Pridgen et al. (2017) found IMC-1 safe and effective and the US Food & Drug Administration (FDA) granted it fast-track designation for development as a fibromyalgia treatment. A newer IMC-1 trial known as FORTRESS began recruiting fibromyalgia patients in 2021.

Itzhaki et al. (2017) has hypothesized that Alzheimer's disease may be caused by viral or bacterial infection, noting "many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1, chlamydia pneumoniae and several types of spirochatete", although there is clear evidence supporting this hypothesis, it is currently not one of the two top hypotheses about the cause of Alzheimer's disease.

Several herpesviruses including HSV-2 may cause false positives on Lyme disease tests.

Hypothesized role in ME/CFS
In a 1993 paper in Medical Hypotheses (journal), P. A. Bond hypothesized that HSV-1 could cause the symptoms of chronic fatigue syndrome (CFS) in a two-stage process Bond analogized to the relationship of HIV to AIDS: as (untreated) HIV weakens the immune system and makes the body vulnerable to opportunistic infections and cancers, which then are recognized as the symptoms of AIDS, Bond suggests a variety of conditions could produce immune dysfunction and consequent vulnerability to HSV-1 (either primary infection or reactivation), which in turn could be the cause of a range of CFS symptoms. In 2006, Bond did a study of 27 CFS patients meeting the Fukuda criteria, and found that antibodies to both HSV-1 and HSV-2 were more common in CFS patients that controls, however a larger study by Blomberg et al. (2019) found levels of HSV-1 and HSV-2 in ME/CFS and fibromyalgia patients were similar to or slightly lower than those of healthy blood donors. The ME/CFS patients were those that met the Canadian Consensus Criteria.

In 2018, Hector Bonilla, MD and Clinical Assistant Professor of Medicine in Infectious Diseases at Stanford University, received a Ramsay Award Grant from the Solve ME/CFS Initiative for a "Cross-sectional study to assess the prevalence of APOE e4 alleles in patients with ME/CFS and the association with herpes virus infection". The project follows on preliminary findings that HSV-1 infection in the sera of individuals with ME/CFS is related to severity of the disease.

Pridgen suggests that an approach related to IMC-1 also merits investigation as an ME/CFS treatment.

News, interviews and articles

 * 2016, Alzheimer's disease could be caused by herpes virus, warn experts - The Telegraph

Notable studies

 * 1993, A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders. (Full text)
 * 1994, Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?
 * 1996, Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.
 * 2002, Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome.
 * 2006, Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport
 * 2013, Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders.