General Features
Herpesviruses are large viruses that comprise double-stranded
DNA enclosed in enveloped icosahedral capsids.
As enveloped viruses, they are vulnerable to acids, detergents, and drying.
Herpes simplex viruses (HSV) cause lifelong infections:
In most cells, they can produce lytic infections.
Cell death is the result of inhibition of macromolecule synthesis, degradation of DNA, disruption of the cytoskeleton, and other disruptions.
In neurons, the virus produces latent infections.
Host inflammatory and cell-mediated responses contribute to the immunopathogenic effects of infection.
HSV evades the host immune system via several mechanisms, including:
— The ability to spread directly from cell-to-cell, which avoids immune cells and molecules;
— HSV has antibody and complement receptors that weaken the effects of innate and humoral immunity;
— HSV can prevent CD8 T cells from recognizing infected cells.
Cowdry type A acidophilic intranuclear inclusion bodies are visible in infected cells; we can see the enlarged, aka, "ballooning" cells. As we'll learn elsewhere, Cowdry inclusion bodies are markers of infection by other herpesviruses, too.
We use a genital infection for our example.
Entry occurs via breaks in the epithelia or mucous membranes.
Replication occurs at the site of entry.
Natural killer and helper T cells may limit the initial infection.
Virions enter nearby neurons, and, via retrograde transport, travel to ganglions.
— In genital HSV infections, the virus travels to the
sacral ganglion
— In
oral HSV infections, the virus travels to the
trigeminal ganglion
Latent infection is established in the ganglion
— It is thought that
CD8 T cells and Interferon-gamma contribute to viral latency.
Reactivation can be triggered by immune suppression, which can be caused by stress, fever, or other factors.
The virus returns to the initial site of infection.
The re-current infection may be asymptomatic or it may produce vesicular lesions that contain fluid and infectious virions.
Transmission:
Close personal contact or contact with secretions from vesicles, the vagina, or saliva.
Vertical transmission can also occur during late pregnancy or childbirth, though this is uncommon.
HSV-1 vs. HSV-2: Both types can cause oral and genital lesions.
HSV-1
Typically, but not always, transmitted orally in the saliva and infects via breaks in the skin.
This type is commonly acquired during childhood.
HSV-2
Typically transmitted sexually.
Most often associated with lesions on the genitalia, anorectal tissues, and oropharynx.
However, be aware that genital lesions caused by HSV-1 are a growing concern.
Herpetic Whitlow is HSV-2 infection on the fingers/thumbs, characterized by small crusted lesion near the fingernail.
Healthcare workers whose hands may come into contact with infected patients or their secretions need to be careful not to contract or spread the virus via their fingers.
HSV-2 infection is associated with an increased risk of HIV co-infection.
Symptoms of HSV infections:
Many individuals are asymptomatic, but may be able to shed the virus.
Many individuals have painful but benign lesions.
Typically, the lesions start out as clear vesicles on red bases that become crusted.
When located around the mouth, they are often called
"cold sores."
When they occur on the genitals, they are called genital lesions.
HSV can also cause
keratoconjunctivitis, which is associated with photophobia, burning pain, itching, and redness.
Most infections are limited by the host's immune system, but immunosuppressed patients and neonates can develop serious infections.
Neonates with HSV can have neurological symptoms, such as seizures; rash, fever, or disseminated disease are also possible.
Review
TORCHeS infection
Immunocompromised patients with HSV viremia can develop disseminated disease, which can involve the liver or other viscera and the central nervous system.
— See an example of
HSV Encephalitis Type 1.
Prevention and treatment of HSV:
Currently no vaccine.
Acylcovir and related antiviral drugs may be given for treatment and prophylaxis.
Healthcare workers should wear gloves to prevent Herpetic Whitlow.
Sexually active individuals should wear male or female condoms to prevent sexual transmission
— Sexual contact should be avoided when lesions are present.
— However, be aware that asymptomatic shedding may still occur.