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Herpes Viruses

Herpes viruses are pervasive, host-adapted pathogens that cause a wide variety of diseases. The term herpes is derived from the Greek word “to creep or crawl,” and dates back to early Greek civilization, approximately 2000 years ago, in reference to the spreading nature of herpetic skin lesions.

Eight types of herpes viruses infect humans. Herpes viruses do not survive long outside a host therefore transmission usually requires intimate contact. The virus is readily inactivated at room temperature and by drying. Little is known regarding the mechanisms by which the virus establishes and maintains in a latent state or is reactivated.

People may get viruses by swallowing or inhaling them, or through intimate personal or sexual contact. Most commonly, viral infections involve the nose, throat, and upper airways. The incubation period for most herpes virus range from two to 12 days. Most people average about three to six days. With the primary infection, the quantity and duration of virus shedding is larger and longer.

Herpes viruses cause cellular and cytoplasmic disruption. Pathologic changes are due to cell necrosis and inflammatory changes. Fluid accumulates between the dermis and the epidermal skin layers, causing vesicle formation. The fluid then is absorbed, scabs are formed, and healing is completed usually without evidence of scarring. Shallow ulcers form after the vesicles rupture on mucous membranes. Lesions from primary herpes infections typically take longer to form and usually persist for a longer duration of time.

Neurovirulence, or the capacity to invade and replicate in the nervous system, is true of all herpes viruses. With viral replication at the site of primary infection, the virus proteins are transported by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. Recurring outbreaks are usually due to some stressor including ultraviolet radiation, fever, trauma, emotional or psychological stress, or immunosuppression. The more severe the primary infection, as revealed by the size, number, and extent of lesions, the more likely it is that recurrences will follow.

Herpes Simplex Virus 1 and 2

There are two types of herpes simplex viruses, both are closely related but differ in epidemiology. Herpes virus 1 (HHV1) is also known as herpes simplex virus 1 (HSV1).  It can be found in saliva, tears, and genital and other secretions. It is typically the cause of cold sores around the mouth. Lesion location, however, is not necessarily indicative of viral type. HSV1 can also lead to infection in the genital area causing genital herpes usually through oral-genital contact. HSV1 infections are highly contagious and are usually spread from skin-to-skin contact with an infected person through small breaks in the skin or mucous membrane. The transmission of herpes simplex virus infection is dependent upon a susceptible seronegative individuals contact with someone excreting HSV. The HSV1 virus may be spread through shared eating utensils, razors, and towels from a person who has an active lesion.

Herpes virus 2 (HHV2) is also called herpes simplex virus 2 (HSV2). It typically causes lesions in the genital, anal and perianal area. It is primarily a sexually transmitted infection. However, it can also cause cold sores in the facial area. Like HSV1, the HSV2 infection is contagious and is spread by skin-to-skin contact even when an active lesion is not noted. In orofacial HSV infections, the trigeminal ganglia are most commonly involved, while, in genital HSV infection, the sacral nerve root ganglia are involved.  After latency is established, a stimulus or stressor can causes reactivation with viral shedding.

Although any herpes virus can cause encephalitis, the HSVs are the most common cause at a rate of 5-10% of cases worldwide.  Disseminated hepatitis and encephalitis caused by HSVs have been seen at increased rates in immunocompromised and pregnant patients. This is thought to be due to the altered immune function during pregnancy allows the systemic disease to develop. It has been suggested that limited T cell function occurs in normal pregnancy to prevent maternal rejection of fetal and placental tissues. These specific immune abnormalities in lymphocytes may facilitate systemic herpes infection.

Neonatal herpes is a rare infection that can be communicated in a variety of ways.  The greatest risk factor appears to be genital herpes (HSV2) in the mother. The neonate may be infected at any point, prenatally, perinatally, or postnatally. Transplacental infection can occur but usually occurs only during the maternal primary infection. Premature rupturing of the membranes is a well-recognized risk factor in the development of neonatal herpes. Transmission during vaginal delivery, in a mother with a primary infection is the greatest threat. There is thought to be a transfer of passive immunity from the mother but it is not always protective.  In a recent study, women with a primary genital infection had a 30-50% chance of transmission to the fetus as compared to 3% chance for those women with recurrent infection.

Herpes virus 3

Herpes virus 3 (HHV3) is also called varicella-zoster virus (VZV). HHV3 causes chickenpox. This virus is most commonly seen in young children and is characterized by itchy vesicular eruptions, low grade fever and malaise. A vaccine is available, but due to the mild symptoms of disease is not frequently give to children under the age of 13. The disease is transmitted by direct contact with skin lesions or more commonly through respiratory droplets from an infected person. This may occur without the patient’s knowledge, making this highly contagious. The vesicular fluid and the scab formations are infectious until completely dried. It can also cause a latent viral infection of the skin, which is called herpes zoster or shingles.

Shingles occurs when dormant varicella-zoster virus from an initial bout with chicken pox becomes reactivated. One out of three people age 60 or older will develop shingles to varying degrees. Like its close relatives, herpes zoster infects skin and nerve cells. This virus may also recur along nerve fiber pathways, causing multiple blisters like sores where nerve fibers end on skin cells. Because an entire group of nerve cells is often affected, shingles is generally much more severe than a recurrence of herpes simplex. The lesions generally appear in a belt-like pattern on one side of the body and are often accompanied by itching, tingling, or even severe pain. Healing usually occurs in 2 to 4 weeks, and scars may remain. Post herpetic neuralgia (PHN) is the pain associated with shingles and can persist for months and even years.

Shingles vaccines have been used since 2006. This vaccine reduces the risk of developing shingles by 51% and PHN by 67%. The vaccine is thought to be good for five years and is approved for those that are over 60. Those with a weakened immune system should not receive this live vaccine.

Herpes virus 4

Herpes virus 4 (HHV4) is also known as the Epstein-Barr virus (EBV). It is the major cause of infectious mononucleosis.  It is a contagious infection and is transmitted through saliva, coughing, sneezing, or sharing eating utensils with an infected person. EBV is found all over the world. Most people get infected with EBV at some point in their lives. EBV can cause a variety of neurological complications that affect the brain, spinal cord and facial nerves. EBV infection can affect a person’s blood and bone marrow. The virus can cause the body to produce an excessive number of lymphocytes leading to lymphomas. There is no rash or skin eruptions seen in EBV, though nasopharyngeal ulcers are common.

Herpes virus 5

Herpes virus 5 (HHV5) is the official name of cytomegalovirus (CMV). CMV is also a cause of mononucleosis. In people with healthy immune systems, the virus may not cause any symptoms.

The most dangerous effect is in the transmission through the placenta infecting newborns. This occurs when a pregnant woman experiences a first-time infection or a reinfection with a different CMV strain or a reactivation of a previous infection during pregnancy. CMV can also be transmitted through sexual contact, body fluids, breast-feeding, blood transfusions and organ transplants. CMV infection in the fetus can cause a small head size, premature labor, intellectual disabilities and an array of neurological problems. About one out of every 150 babies is born with congenital CMV infection. However, only about one in five babies with congenital CMV infection will be sick from the virus or will have long-term health problems.

CMV infection is one of the most difficult complications of AIDS. It may lead to diarrhea, severe vision problems including blindness, infections of the stomach and intestines and death. Though this virus barely causes a problem in most people with healthy immune systems, it can be devastating in people with damaged immune systems.

Herpes virus 6

Herpes virus 6 (HHV6) has been observed in the blood cells of a few patients with a variety of diseases. HHV6 causes roseola, resulting in a high fever and skin rash in small children. It is contagious from about two days before the fever starts until 1 or 2 days after the fever is gone, even if the rash continues. It is only mildly contagious and appears to be spread by direct contact and respiratory fluids with an infected person. This infection accounts for many of the cases of convulsions (febrile seizures) associated with fever in infancy. There are not vesicular eruptions with HHV6.  After primary infection, HHV6 remains latent in lymphocytes and monocytes and persists at low levels in cells and tissues.

In healthy adults, this infection is generally of no consequence. In patients infected with HIV, HHV6 infection may increase HIV replication and hasten the progression toward AIDS. HHV6 also has been implicated in the development of white-matter demyelination in persons with AIDS, leading to dementia.

Herpes virus 7

Herpes virus 7 (HHV7) is even more recently observed and is closely related to HHV6. Like other herpes viruses, HHV6 and HHV7 are so common that most of humanity has been infected at some point, usually early in life. The virus is spread by saliva with no know specific clinical syndrome.  HHV7 can also cause roseola, but it is not clear what other clinical effects that this virus causes.

Herpes virus 8

Herpes virus 8 (HHV8) was recently discovered in the tumors of Kaposi’s sarcoma (KSHV). KSHV is thought to be due to an infection that has been around for decades, but was only successfully grown directly from tumors. It was found by isolating its DNA directly from a KS tumor without growing the virus in the laboratory. These tumors are found in people with AIDS and are otherwise very rare.  HHV8 is primarily sexually transmitted but has been seen in cases of IV drug use. KSHV forms purplish tumors in the skin and other tissues of some people with AIDS. It is very difficult to treat. HHV8 may also cause other cancers, including certain lymphomas in those with failing immune systems.

The discovery of more strains of herpes viruses is inevitable. Learning the way these viruses affect other organs and incite disease may allow researchers to block their replication. Additional vaccines and antiviral medications are in development to hopefully decrease the spread of these diseases. No FDA-cleared polymerase chain reaction (PCR) test to diagnose herpes is available in the United States. Health-care providers frequently must treat patients before test results are available to curb the possibility of ongoing transmission and lessen the incidence of complications.

References:

Babies Born with CMV (Congenital CMV Infection). Retrieved from https://www.cdc.gov/cmv/congenital-infection.html. 

Kohn, Melissa. (2017). Herpes Simplex in Emergency Medicine. Medscape. Retrieved from http://emedicine.medscape.com/article/783113-overview. 

NIH launches trial of investigative genital herpes vaccine. (2013). Retrieved from https://www.nih.gov/news-events/news-releases/nih-launches-trial-investi….

Shingles (Herpes Zoster). Retrieved from https://www.cdc.gov/shingles/.