[6] Symptoms, when they occur, may include watery blisters in the skin of any location of the body, or in mucous membranes of the mouth, lips, nose, genitals,[1] or eyes (herpes simplex keratitis).

[11] Studies on discordant partners (one infected with HSV-2, one not) show that the transmission rate is approximately 5–8.9 per 10,000 sexual contacts, with condom usage greatly reducing the risk of acquisition.

The risk is considerable when the mother is infected with the virus for the first time during late pregnancy, reflecting a high viral load.

An example of this is herpetic whitlow, which is a herpes infection on the fingers; it was commonly found on dental surgeon's hands before the routine use of gloves when treating patients.

For instance, one of the first functional promoters in eukaryotes was discovered in HSV (of the thymidine kinase gene) and the virion protein VP16 is one of the most-studied transcriptional activators.

Early gene expression follows, to allow the synthesis of enzymes involved in DNA replication and the production of certain envelope glycoproteins.

Interactions of these molecules then form a stable entry pore through which the viral envelope contents are introduced to the host cell.

The nectin receptors usually produce cell-cell adhesion, to provide a strong point of attachment for the virus to the host cell.

Once bound to the HVEM, gD changes its conformation and interacts with viral glycoproteins H (gH) and L (gL), which form a complex.

[39] HSV usually produces cytopathic effect (CPE) within 24–72 hours post-infection in permissive cell lines which is observed by classical plaque formation.

However, HSV-1 clinical isolates have also been reported that did not show any CPE in Vero and A549 cell cultures over several passages with low levels of virus protein expression.

Probably these HSV-1 isolates are evolving towards a more "cryptic" form to establish chronic infection thereby unravelling yet another strategy to evade the host immune system, besides neuronal latency.

[40] Following the infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, is produced.

Research using flow cytometry on another member of the herpes virus family, Kaposi's sarcoma-associated herpesvirus, indicates the possibility of an additional lytic stage, delayed-late.

By maintaining the host cells, LAT expression preserves a reservoir of the virus, which allows subsequent, usually symptomatic, periodic recurrences or "outbreaks" characteristic of non-latency.

[citation needed] A protein found in neurons may bind to herpes virus DNA and regulate latency.

[26] For instance, VP16 plays an important role in IE transcription and the virus particle brings it into the host cell, so that it does not need to be produced first.

[26] Importantly, HSV shuts down host cell RNA, DNA, and protein synthesis to direct cellular resources to virus production.

[58] The East Asian HSV-1 isolates have an unusual pattern that is currently best explained by the two waves of migration responsible for the peopling of Japan.

[61] Another analysis has estimated the mutation rate in the herpes simplex 1 genome to be 1.82×10−8 nucleotide substitution per site per year.

[60] Similar to other herpesviridae, the herpes simplex viruses establish latent lifelong infection, and thus cannot be eradicated from the body with current treatments.

[63] Treatment usually involves general-purpose antiviral drugs that interfere with viral replication, reduce the physical severity of outbreak-associated lesions, and lower the chance of transmission to others.

Studies of vulnerable patient populations have indicated that daily use of antivirals such as aciclovir[64] and valaciclovir can reduce reactivation rates.

In January 2020, a comprehensive review article was published that demonstrated the effectiveness of natural products as promising anti-HSV drugs.

[79] Thus it appears that the HSV genome may be subjected to oxidative DNA damage during infection, and that MR may enhance viral survival and virulence under these conditions.

[citation needed] Modified Herpes simplex virus is considered as a potential therapy for cancer and has been extensively clinically tested to assess its oncolytic (cancer-killing) ability.

[80] Interim overall survival data from Amgen's phase 3 trial of a genetically attenuated herpes virus suggests efficacy against melanoma.

[84] Herpes simplex viruses have also been studied in the central nervous system disorders such as multiple sclerosis, but research has been conflicting and inconclusive.

In addition to offering antiviral medication to alleviate symptoms and shorten their duration, physicians must also address the mental health impact of a new diagnosis.

As of 2022, there are active pre-clinical and clinical studies underway on herpes simplex in humans; vaccines are being developed for both treatment and prevention.