top of page
Part of a young woman's face with a virus herpes on lips, treatment with ointment.jpg

herpes simplex lATeNCY

Herpes Simplex Latency refers to a dormant state of the herpes simplex virus (HSV) including:

 

  • Herpes Simplex Virus 1 - Cold sores 

  • Herpes Simplex Virus 2 - Genital Herpes

 

Unlike most viruses that are eliminated by the immune system after the initial infection, Herpes Simplex persists by entering a dormant state within specific sensory neurons. For HSV-1, it is a cluster of nerves within the face, mouth, and eyes, HSV 1 can also be relocated to genitals nerves on contact. For HSV-2 it lays dormant within nerves of the genital and perianal regions.

 

During a latent phase, herpes simplex halts replication and does not produce infectious particles. Instead, its genome silently remains within the infected cell. This stealth mode allows the virus to remain by evading immune surveillance. However, under certain physiological or environmental triggers, these viruses can reactivate, reinitiating replication, spreading to new cells, and potentially being transmitted to others.

 

Reactivation is not an uncommon event, in fact Herpes Simplex can reactivate on a daily or near-daily basis, leading to viral shedding in saliva or genital secretions, even in the absence of clinical symptoms. This means that herpesvirus latency is not as static as one thinks, but rather a regular and cyclical process 

 

Despite the high frequency of viral reactivation, only a small proportion of latently infected cells become active at any given moment. This low-level, intermittent reactivation allows the virus to evade complete immune clearance, thereby sustaining lifelong infection and contributing to a persistent, low-grade immune response. 

 

In any given episode of HSV reactivation, if the immune system responds promptly and effectively, the virus is usually contained before it can cause noticeable damage. In such cases, the individual may experience no outward symptoms at all, or only mild sensations such as tingling, itching, or slight discomfort. 

 

However, when the immune defense mechanisms are compromised, the virus is able to replicate more freely. This unchecked replication leads to the destruction of epithelial cells, resulting in the formation of painful blisters or ulcers, typically seen on mucosal surfaces such as the lips, genitals, or eyes. These symptomatic outbreaks not only cause physical discomfort but also increase the risk of transmitting the virus to others.

signs & symptoms

HSV-1 Signs and Symptoms

 

Cold Sores

 

Cold sores is the most frequent clinical presentation of HSV-1. While many individuals experience asymptomatic infection, symptomatic cases typically involve painful, grouped vesicles on an erythematous base affecting the lips and mouth. 

 

Lesions follow a characteristic progression from vesicles to pustules and ulcers, which crust and heal within two to six weeks. Recurrent infections are usually milder, beginning with a 24-hour prodrome of tingling, itching, or burning [5].

​

HSV-2 Signs and Symptoms

 

Genital Lesions

 

The most characteristic presentation of HSV-2 involves genital lesions, often appearing as painful blisters, ulcers or sores in the genital area. These lesions can be extremely painful, especially in women, where vulvar swelling may also occur. Additional local symptoms include tingling, intense itching, burning sensations and dysuria (painful urination). These symptoms can persist for up to three weeks if untreated. 

 

Vaginal Itching 

 

Vaginal itching caused by herpes simplex virus type 2  is primarily the result of nerve irritation and local inflammation triggered by viral activity in the genital region. When HSV-2 reactivates from latency in the sensory nerve ganglia, it travels back along the nerves to the skin and mucosal surfaces, particularly around the vagina and vulva. This movement stimulates nearby nerve endings, producing sensations of itching, tingling, or burning often before any visible lesions appear. 

 

In some cases, women may experience itching during asymptomatic viral shedding, when no outward sores are visible, but the virus is still active at a microscopic level. Thus, vaginal itching is a common and important early indicator of HSV-2 activity, even in the absence of obvious skin changes. [12]

 

Dysuria 

 

Dysurina, is a burning sensation during urination in HSV-2 occurs when urine touches herpes-related ulcers or inflamed tissue, or when the urethra itself is irritated by viral infection. [12]

Causes

HSV-1 Reactivation Causes - Coldsores

 

Physical or Psychological stress [ SNS Hyperactivity ]

 

Adrenaline, a hormone released during both physical or psychological stress, can specifically reactivate HSV-1 in nerve cells. This happens when adrenaline binds to β-adrenergic receptors on neurons, triggering a molecular chain reaction called the cAMP–PKA–CREB signaling pathway. This pathway activates the virus’s immediate-early genes, which are essential for restarting the viral lifecycle.

 

At the same time, adrenaline causes epigenetic remodeling, meaning it changes how the virus’s genetic material is packaged. Specifically, it removes repressive chemical markers from the viral DNA, making it easier to access and turn on.[1][2]

 

Elevated Cortisol [ Hypercortisolism ] 

 

Elevated cortisol plays a major role in reactivating herpes simplex virus, especially HSV-1. This is because cortisol binds to specialized proteins in neurons called glucocorticoid receptors (GRs). This hormone–receptor pair then moves into the nucleus, the control center of the cell, where it modifies the activity of both human and viral genes.

 

For HSV-1, one key change is the reduction in latency-associated transcripts, which normally help keep the virus in a dormant state. At the same time, the activated GRs stimulate expression of viral immediate-early (IE) genes, which kickstart the virus’s active replication cycle.[1][2]

 

Immune Impairments [ Tregs Dysfunction ] 


Herpes simplex virus outbreaks are controlled by the body’s immune system, and one of the most important players in this defense are regulatory T-cells (Tregs). These cells act as coordinators, making sure the immune system responds strongly enough to clear the virus but also in the right way. Research shows that when Tregs are missing or not working properly, HSV spreads more quickly, viral levels stay higher, and the infection can even reach the nervous system earlier.

Tregs do this by helping dendritic cells, the messengers of the immune system, to travel from the infected tissue to the nearby lymph nodes, where they show viral fragments to CD4 T-cells. This ‘priming’ step is crucial, without it, CD4 T-cells don’t multiply or move into the infected tissue properly, which means the virus isn’t controlled. A key part of this process relies on a molecule called CTLA-4, which Tregs use to regulate dendritic cell migration and ensure the right communication happens.

 

Simply, if Treg numbers are too low, or their function is impaired, the immune system can’t get its CD4 T-cells into position to fight HSV. This makes outbreaks more severe and harder to control. [13]

 

Heavy Metal Toxicity

 

Exposure to heavy metals, specifically lead, cadmium, and mercury has been significantly linked to a higher risk of herpes simplex virus type 1 infection, with a 25% increased risk of reactivation [4].

 

Mechanistically, heavy metals weaken the immune system through multiple pathways, disrupting cytokine signaling, impairing immune cell maturation, and inducing oxidative stress, DNA damage, and apoptosis. 

 

These disruptions can reduce the body's ability to suppress latent viruses like HSV, allowing them to reactivate more easily. Specifically, Lead and Mercury, which are known to affect the nervous system, where HSV-1 resides latently.[2][3]

 

UV Light

 

UV light exposure can trigger the cell’s DNA damage response, a repair mechanism that inadvertently lifts the molecular "brakes" keeping the virus dormant. This de-repression of the latent viral genome can initiate reactivation.

 

Intense Exercise and Heat

 

Intense exercise, heat therapies or fever can activate heat shock proteins (HSPs). HSPs influence viral gene expression as they can act as chaperones that modulate chromatin structure and potentially unmask immediate-early gene promoters (like ICP0), helping the virus re-enter the lytic cycle.[1]


HSV-2 Reactivation Causes - Genital Herpes

 

Herpes Simplex Virus 2 shares the same primary reactivation triggers as HSV-1, with exception to UV light exposure. This is due to its similar ability to establish latency in sensory neurons. In addition to the causes established in HSV-1, further causes include: 

 

Genital trauma or irritation

 

Herpes simplex virus type 2  establishes lifelong latency in the sacral dorsal root ganglia, a cluster of sensory neurons that reside within the genital and perianal regions. These neurons harbor the virus in a dormant state after the initial infection.

 

When the genital area experiences mechanical stress, be it from sexual intercourse or otherwise, it can cause local inflammation, tissue damage, and sensory nerve stimulation. This, in turn, may activate intracellular stress responses within infected neurons, which is known to influence the cAMP–PKA pathway, which is capable of initiating immediate-early gene expression of the virus, encouraging reactivation.[1]


Hormonal fluctuations 

 

Menstruation and hormonal fluctuations are well-documented HSV-2 clinical triggers. It has been clinically observed that HSV-2 reactivation and viral shedding are more frequent in the luteal phase (high progesterone) of the menstrual cycle. This is due to Progesterone inducing thinning of the vaginal epithelium and altering mucosal immunity, in turn decreasing barrier protection, allowing easier viral access to neurons.[1]

bottom of page