Herpes Simplex Virus: Causes, Symptoms, Treatment

Herpes simplex virus (HSV) causes common infections of the skin, mouth, eyes, and genitals in humans. Once infected, the virus settles into the nerve roots and persists for life as a latent infection that occasionally reactivates and causes symptoms.[1][2]

There are two strains of the virus. HSV-1 is more common and usually infects the face, while HSV-2 is less common and usually infects the genitals. However, either strain can infect the face or genitals.[2]

Infections are more common in women than men and often have no symptoms. There is currently no licensed vaccine or cure for HSV.[1][2][3]

How common is herpes?

As of 2016, 48% of Americans aged 14-49 had HSV-1 while 12% had HSV-2. The incidence of both strains has declined slightly since 1999.[3]

Prevalence of both strains increases with age and differs across racial populations. HSV-1 is most common in Mexican-Americans, with at least 72% infected, while HSV-2 is most common in blacks, with at least 35% infected.[3]

HSV-1 is slightly more common in women (51% of women vs 45% of men), but women have twice the rate of infection for HSV-2 (16% of women vs 8% of men). This difference is likely because genital infections are more easily transmitted from men to women during vaginal sex than from women to men.[2][3]

Herpes types

Each strain of HSV has slightly different characteristics, however, they cause indistinguishable facial or genital lesions.[1]

  • Herpes simplex virus type 1 (HSV-1) – This strain usually infects the trigeminal nerve root near the mouth. Oral HSV-1 is typically acquired in childhood which gives future protection to being infected genitally. However, because oral HSV-1 infections have declined in recent decades, people have become more susceptible to contracting the virus genitally and those infections are increasing. Having HSV-1 infection may mean that HSV-2 infection will not be as symptomatic or recur as frequently.[1][2][3][4]
  • Herpes simplex virus type 2 (HSV-2) – This strain usually infects the sacral nerve root near the genitals and is acquired sexually. HSV-2 causes symptomatic genital recurrences at a much higher rate than HSV-1. This may be because HSV-1 is less likely to result in latent infection of the sacral nerve root and there may be biological differences in the ability to develop such an infection.[1][2][5]

How is herpes spread?

HSV can be shed from normal-appearing skin and be in oral and genital fluids. Condoms and antiviral drugs can help prevent transmission. In the United States, an estimated 87% of 14-49 year-olds infected with HSV-2 have never received a clinical diagnosis.[2][3]

Generally, a person can only get HSV-2 infection during genital contact with someone who has a genital HSV-2 infection. However, receiving oral sex from a person with an oral HSV-1 infection can result in getting a genital HSV-1 infection.[2]

In people with symptomatic HSV-2 infections, shedding of the virus occurs on 20% of days, compared to 10% of days among those without symptoms.[2]

A weakened immune system can make transmission and symptoms more likely. One interesting example is herpes virus reactivation in astronauts during space flights due to the environment that stresses their immune system.[6]

Symptoms of infection

People with symptoms may have painful blisters or sores at the site of infection, however, most individuals infected with HSV are asymptomatic or have mild symptoms that are mistaken for another skin condition.[2][3]

People with suppressed immune function are at risk for systemic or disseminated infections that may require emergency care and antiviral therapy.[7][8]

The average time between infection and symptoms for an initial herpes infection is 4 days after exposure. Symptoms of genital herpes differ between the first and subsequent outbreaks.[2]

  • First outbreak – The first outbreak of herpes is often associated with a longer duration of blisters and sores, increased viral shedding (making HSV transmission more likely) and systemic symptoms including fever, body aches, swollen lymph nodes, or headache.[2]
  • Recurrent outbreaks – Subsequent outbreaks of genital herpes are common, and many patients recognize early warnings such as genital pain, tingling, or shooting pains in the legs which occur hours to days before the symptoms appear. Recurrent outbreaks are typically shorter and less severe than the initial outbreak of genital herpes. Long-term studies have indicated that the number of symptomatic recurrent outbreaks may decrease over time. Also, recurrences and viral shedding are much less frequent for genital HSV-1 infection than for genital HSV-2 infection.[2]

Risks of having herpes

  • May make it easier to spread HIV – Genital herpes can cause breaks in the skin and increase cells that HIV target for entry.[2]
  • Can be passed to infants – Genital herpes can be passed to infants and is potentially deadly.[9]
  • Can cause brain swelling – Rarely, herpes can cause inflammation of the brain (encephalitis). It is treated with antivirals like Acyclovir or Foscarnet but resistant strains are emerging.[10]

Alzheimer's disease and herpes

New research has indicated a connection between Alzheimer's and HSV infection. Detectible presence of HSV in the bloodstream increases with age and the virus can invade many brain regions.[11]

HSV receptors are abundant in the hippocampus, a site of early degeneration in Alzheimer's Disease, and the virus has been found in the brain of people with the disease.[11]

In one large study, there was an association between HSV and declining memory function, especially among carriers of the APOE e4 gene. The results strengthen the hypothesis that HSV is associated with Alzheimer's development.[12]

  • Declining immune system – There are suggestions that a declining immune system in the elderly might predispose to virus reactivation. The immune system undergoes systemic changes over a lifetime and reactivation of HSV has been reported to take place as a function of age.[11]
  • Autoimmune reaction – HSV could initiate an autoimmune reaction against the body's nerve cells which may have implications for Parkinson's and Alzheimer's Disease. Nerve cells have proteins that resemble portions of the virus from a structural and genetic standpoint.[13]

Herpes treatment

No vaccines or cure for herpes currently exist, so the most common treatment is antiviral drugs that reduce symptoms and likelihood of transmission.

  • Antivirals – Antiviral drugs like Acyclovir or Foscarnet can alleviate the symptoms of herpes infection and speed the healing process. In addition, they can reduce recurrences when used for suppressive therapy. However, these drugs do not decrease the frequency of subsequent recurrences.[1]

Future research

  • Butylated hydroxytoluene (BHT) – BHT is a compound with activity against many viruses, including herpes simplex virus. Not many studies exist, but two show promising results. The effect of 15% BHT in mineral oil on recurrent facial herpes showed lessened duration of blisters, time to scab formation, and virus shedding. In genital herpes, BHT lesion duration was reduced.[16][17]
  • Amino acids – It has been hypothesized that lysine, an essential amino acid widely available as a supplement, can inhibit the growth of herpes. In a review of the research, lysine supplementation appeared to be ineffective in doses less than 1 gram/day, but doses above 3 grams improved patients’ subjective experience of the disease. Longer duration studies of daily lysine are needed.[18]
  • Stem cells – One study of mice suggests that mesenchymal stem cell therapy enhances immune response and protects against herpes infection. Therefore, stem cells may be an approach towards the development of effective management of generalized HSV infection.[14]
  • Frog skin – Molecules secreted in the skin of frogs (temporins) have antiviral properties and may be useful in the development of new HSV therapies.[15]