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Herpes Simplex Virus

Herpes simplex virus (HSV) encompasses two main species: HSV-1 and HSV-2, known scientifically as Human alphaherpesvirus 1 and Human alphaherpesvirus 2, respectively. Both viruses belong to the Herpesviridae family, which causes viral infections in humans.

HSV-1 primarily causes oral herpes, while HSV-2 mainly leads to genital herpes. Both are highly contagious and prevalent worldwide.

Symptoms

HSV infections are often asymptomatic, but when symptoms do occur, they typically manifest as watery blisters on the skin or mucous membranes, such as the mouth, lips, nose, genitals, or eyes. These blisters heal with a scab characteristic of herpetic disease. HSV-1 and HSV-2 are neurotropic and neuroinvasive, meaning they persist in the body by hiding in neurons. After the primary infection, sporadic viral reactivations can occur, leading to outbreaks where new sores may develop.

Transmission

Transmission occurs through contact with an infected person who is shedding the virus, which can happen even asymptomatically. HSV-1 is often acquired orally in childhood but can also be sexually transmitted. HSV-2 is generally a sexually transmitted infection but can also be transmitted from mother to child during childbirth. The virus can survive on surfaces for up to 4.5 hours, allowing for potential transmission through shared objects like towels and toothbrushes.

TEM micrograph of virions of a herpes simplex virus species
TEM micrograph of virions of a herpes simplex virus species

Virology

HSV has a double-stranded DNA genome encased in an icosahedral capsid, surrounded by a lipid bilayer envelope. The virus contains 74 known genes, which encode various proteins involved in forming the capsid, tegument, and envelope, and in controlling replication and infectivity.

Viral Structure

3D reconstruction of the HSV-1 capsid
3D reconstruction of the HSV-1 capsid
Herpes simplex virus 2 capsid
Herpes simplex virus 2 capsid

Cellular Entry

HSV enters host cells through glycoproteins on its surface binding to cell surface receptors. This binding induces membrane fusion, allowing viral contents to enter the host cell.

A simplified diagram of HSV replication
A simplified diagram of HSV replication

Replication and Latency

After entering the cell, HSV expresses immediate early genes, followed by early and late genes, leading to viral replication. The virus can also establish latency, particularly in neural ganglia, where it remains dormant until reactivation.

Micrograph showing the viral cytopathic effect of HSV
Micrograph showing the viral cytopathic effect of HSV (multinucleation, ground glass chromatin).

Treatment

HSV infections are lifelong, with no current treatment capable of eradicating the virus. Antiviral drugs like aciclovir and valaciclovir are used to manage symptoms, reduce the severity of outbreaks, and lower transmission risk. Drug resistance can occur, necessitating ongoing research into new treatments.

Alzheimer's Disease Link

Research suggests a possible link between HSV-1 and Alzheimer's disease, particularly in individuals with the epsilon4 allele of the APOE gene. HSV-1 may increase the risk of Alzheimer's by interacting with lipoprotein components and receptors, leading to the development of the disease.

Use as an Anti-Cancer Agent

Modified HSV is being looked at as a potential cancer therapy due to its ability to kill cancer cells. Clinical trials are ongoing to assess its efficacy against various cancers, including melanoma.

Neuronal Connection Tracing

HSV is also used in neuroscience research as a transneuronal tracer to map neuronal connections by crossing synapses.

Other Related Outcomes

HSV-2 is a common cause of Mollaret's meningitis, while HSV-1 can lead to herpes simplex encephalitis. There is also ongoing research into its potential involvement in other central nervous system disorders, such as multiple sclerosis.

Research

Despite vaccines for other herpesviruses, no vaccine exists for HSV. Research is ongoing to develop vaccines for treatment and prevention, with several pre-clinical and clinical studies underway.

HSV replication cycle
HSV replication cycle

Self-assessment MCQs (single best answer)

Which family does the Herpes Simplex Virus (HSV) belong to?



What is the primary cause of oral herpes?



How does HSV typically manifest when symptoms occur?



Through what primary mode is HSV-2 generally transmitted?



What is the structure surrounding HSV's DNA genome?



Where does HSV establish latency in the body?



Which antiviral drugs are commonly used to manage HSV infections?



HSV has been linked to which neurodegenerative disease, particularly in individuals with the epsilon4 allele of the APOE gene?



Which technique is HSV used for in neuroscience research?



What is Mollaret's meningitis commonly associated with?



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