Human Herpesvirus (HHV)
Written by Ada’s Medical Knowledge Team
What is Human Herpesvirus?
The herpesvirus family is a group of viruses that can infect both animals and humans. Over 130 species of herpesvirus are known, but only eight of these are known to infect humans. These, collectively, are known as human herpesvirus, or HHV.
The herpesvirus family are DNA viruses, which means that they have DNA rather than RNA as their genetic material (the HIV virus, for example, is an RNA virus). Other DNA viruses that affect humans are adenoviruses,different types of which can cause the common cold, conjunctivitis and bronchitis, as well as human papillomaviruses, various strains of which can cause warts, genital warts, cervical cancer, and anal cancer. It is important to note that, although these are all DNA viruses, they are not otherwise related to one another.
Human herpesviruses are contagious, which means that they are passed from person to person. Because they do not live for long outside the human body, they are usually passed on by direct contact with bodily fluids, rather than infected objects. Human herpesviruses can be passed on by:
- Respiratory secretions, such as phlegm from a cough or water droplets from a sneeze
- Sexual intercourse
- Direct skin contact with a rash caused by an HHV infection
Newborn babies can be infected in the womb or during birth.
The human herpesvirus family is the source of many common diseases, including chickenpox, shingles, mononucleosis, cold sores and genital herpes. Infections caused by human herpesvirus tend to remain latent, which means they stay in the host even after the primary infection has resolved and can reactivate later.
Viruses in the Human Herpesvirus family
Only eight members of the herpesvirus are known to infect humans, which is why they are known as human herpesviruses. Some of these viruses have more than one name. The eight herpesviruses that infect humans are:
- Human Herpesvirus 1 (HHV-1), also known as Herpes Simplex Virus 1 (HSV-1)
- Human Herpesvirus 2 (HHV-2), also known as Herpes Simplex Virus 2 (HSV-2)
- Human Herpesvirus 3 (HHV-3), also known as Varicella Zoster Virus (VZV)
- Human Herpesvirus 4 (HHV-4), also known as Epstein-Barr Virus (EBV)
- Human Herpesvirus 5 (HHV-5), also known as Cytomegalovirus (CMV)
- Human Herpesvirus 6 (HHV-6)
- Human Herpesvirus 7 (HHV-7)
- Human Herpesvirus 8 (HHV-8), also known as Kaposi’s Sarcoma-associated Herpesvirus (KSHV)
Because referring to these viruses can become confusing due to the similarity of the names, this document will use the alternative names. For example, human herpesvirus 1 will be called herpes simplex virus 1 or HSV-1, and human herpesvirus 4 will be called Epstein-Barr Virus or EBV.
HHV-1 and HHV-2: Herpes Simplex Virus
Human Herpes Virus 1 and 2 are also known as Herpes Simplex Virus 1 and 2. They are extremely common, with HSV-1 being present in 90 percent of adults and HSV-2 being present in between ten and 30 percent of adults. HSV-1 is usually associated with herpes labialis, but can sometimes cause genital herpes, while HSV-2 is usually associated only with genital herpes.
Most people are infected with HSV-1 during early childhood, and symptoms are mild; some children may not show any symptoms at all. HSV-1 is spread by saliva and/or respiratory secretions, but HSV-2 is almost always spread by genital contact. People usually contract HSV-2 later in life than they contract HSV-1. However, in the U.S.A., Europe and some parts of the western Pacific, it is becoming more common to contract HSV-1 for the first time during sexual activity as a teenager or adult, which is leading to an increase in the number of cases of genital herpes caused by HSV-1.
Herpes labialis, also known as oral herpes, cold sores or fever blisters, is caused by HSV-1. It is characterized by recurrent outbreaks of painful blisters on the lips and is highly contagious. People with an active outbreak of herpes labialis, i.e who have an active cold sore, should avoid kissing or oral sex. Stress, illness or weather conditions may trigger the appearance of cold sores.
Herpes labialis is not usually very serious, although people with weak immune systems are more at risk of complications.
Genital herpes is characterized by itchy painful blisters on the genitals and in the genital region. It is usually caused by HSV-2 and is almost always sexually transmitted. For this reason, anyone with an active blister caused by genital herpes should refrain from sexual activity until the blister has healed. Like cold sores, outbreaks of genital herpes can be triggered by stress, illness or weather conditions.
Most babies who are born to mothers who have HSV-1 or HSV-2 are not at all affected by it, but if the mother contracts HSV for the first time during the third trimester of pregnancy, the chances of the baby experiencing complications is increased. HSV infection in very young babies, or newborns, is known as neonatal herpes.
The majority of cases of neonatal herpes happen when the baby is exposed to the virus in the birth canal during delivery. The affected baby usually begins to show symptoms during the first month of life.
There are three main subcategories of neonatal herpes:
Skin infection, in which a rash forms on the skin and around the eyes and mouth Encephalitis, inflammation of the brain which can cause problems such as seizures Disseminated infection, in which the virus spreads throughout the body and affects various organs
- Loss of appetite or unwillingness to feed
- Blisters anywhere on the body, including the eyes and mouth
- Difficulty breathing, such as grunting, rapid breathing, irregular breathing or a bluish appearance
Neonatal herpes is rare, but is considered an emergency, and medical attention should be sought as soon as symptoms appear.
HHV-3: Varicella Zoster Virus
The varicella zoster virus, also known as VZV, herpes zoster and sometimes simply as zoster, causes the common childhood disease chickenpox, when it infects a person for the first time and, when reactivated later in life, causes the painful skin condition known as shingles.
Although chickenpox is a common disease, its incidence is falling due to effective widespread vaccination campaigns in most developed countries. Nevertheless, it is a common childhood condition, with outbreaks periodically happening at kindergartens and elementary schools. It is also common for the siblings, parents or caregivers of an affected child to contract the virus, especially if they have not been vaccinated. The condition tends to be more severe among teenagers and adults, but relatively mild in children.
The most distinctive symptom of chickenpox is an itchy, blister-like rash. Other symptoms include fever, headache and body aches, which often appear before the rash develops. The outlook in cases of chickenpox is usually good, and most people recover without particular treatment. Complications can develop, but these are not common. Potential complications include pneumonia, secondary bacterial infections, and, more rarely, encephalitis.
Shingles: varicella zoster
After the primary varicella zoster infection has resolved, the varicella virus remains dormant in the body for life. It can be reactivated later in life by stress or illness. Older adults and those with weakened immune systems may be more at risk of developing shingles.
When the virus reactivates, it travels up the nerve in which it has lain dormant to the surface of the skin, causing painful lesions. These are usually restricted to an area of the skin served by a particular nerve, known as a dermatome, leading to a characteristic stripe pattern of lesions.
Shingles is very uncomfortable and may become complicated if it affects the ears or eyes, or if a secondary bacterial infection affects the lesions and leads to a skin infection.
Shingles is treated with antiviral medications and pain management medications, and most people recover well within two weeks. Some, however, experience ongoing pain and discomfort in the affected area; this is known as post-herpetic neuralgia.
HHV-4: Epstein-Barr Virus
It is estimated that about 90% of the world’s entire population carries the Epstein-Barr virus (EBV). Most people contract the virus in childhood, when symptoms of infection are mild and often go unnoticed.
The Epstein-Barr virus remains in the body for life. Periodically, people with EBV shed the virus in their bodily fluids and tissues. When this happens, people who come into contact with their saliva or respiratory droplets may contract the virus. It is possible to have EBV and not know it.
Although most people who contract EBV remain asymptomatic for life, some may develop a condition known as infectious mononucleosis, which is also called glandular fever or simply mono. This is more common in people who encounter EBV for the first time during adolescence or early adulthood.
The main features of this condition are fatigue and a severe sore throat. The fatigue associated with infectious mononucleosis can last up to six months in extreme cases, but usually resolves after three months. Most people recover well, but complications can develop. These include encephalitis, a ruptured spleen and extremely enlarged tonsils.
Cytomegalovirus, like other members of the human herpesvirus family, is commonly found worldwide. In most people, the virus lies dormant in the body once the original infection has cleared up and can be reactivated by stress or illness.
Infection with cytomegalovirus (CMV) is extremely common, and it is estimated that between 60 and 90 percent of all adults have had CMV at some time in their lives. Usually, the virus is contracted during childhood, though it is also possible to be infected for the first time as an adult. In adolescents and adults, CMV infection may cause CMV mononucleosis, which is similar to EBV mononucleosis. In healthy people, CMV infection is often asymptomatic or has only mild, non-specific symptoms such as fever, malaise and swollen lymph glands.
Most people who have CMV will have no ill-effects, but people with weakened immune systems may experience serious complications. Likewise, babies born to mothers who are infected with CMV for the first time during pregnancy may develop congenital cytomegalovirus infection, which can be very serious.
Human herpesvirus 6 is quite commonly found in the human population, affecting between 25 and 95 percent of many populations. Most people contract HHV-6 by the age of three years, and in the majority of cases, the infection is asymptomatic. By far the most common strain of HHV-6 is HHV-6B, which is implicated in the vast majority of all HHV-6 infections, including the common childhood condition roseola infantum. HHV-6A is much less common and is usually found in people with weakened immune systems, for example people affected by HIV infection or chemotherapy.
HHV-6 is spread from person to person by contact with respiratory secretions from coughing or sneezing. Like all strains of human herpesvirus, HHV-6 causes a primary infection, such as roseola infantum, and then stays latent in the body, where it can be reactivated by stress or other illness. In some adults who experience a primary infection of HHV-6, a mononucleosis-like condition can develop.
It is much more common for HHV-6 reactivation to happen in people with weakened immune systems than those with normal immune systems. When the virus reactives, it can affect any organ, including the heart, lungs, kidneys and brain. If the brain is involved, complications such as otitis media, hepatitis and encephalitis may occur.
In most cases, HHV-6 infection is an uncomplicated condition that clears up on its own. Laboratory tests are not usually needed to diagnose a primary infection, but are sometimes used to identify HHV-6 reactivation in people with weakened immune systems.
There is no specific treatment for HHV-6 infection  but some evidence shows that antivirals such as ganciclovir, cidofovir and foscarnet may be useful in some cases. Antivirals should be used in cases of HHV-6 primary infection or reactivation in people with compromised immune systems.
Roseola infantum is a common childhood condition, caused by infection with HHV-6, that causes high fever, irritability, loss of appetite and a rash. It is most common in children between the ages of six months and two years, but can affect adults, though symptoms tend to be mild in both cases. It is the primary infection caused by human herpesvirus 6, in the same way that chickenpox is the primary infection of HHV-3, the chickenpox virus. HHV-7 can also sometimes cause roseola infantum.
A common complication of roseola infantum is febrile seizures,** which can sometimes require hospitalization, but are usually passing and not an indication of epilepsy. It is rare for an adult or a child to have roseola more than once, but this can happen if the affected person is immunosuppressed.
HHV-7, like HHV-6, affects upwards of 90 percent of all adults worldwide. Infection with HHV-7 usually occurs in childhood or infancy, and is usually asymptomatic. The conditions caused by this human herpesvirus are generally less well-understood overall than those caused by some of the other strains of the virus.
In children, primary infection with HHV-7 can cause a fever, on its own or in combination with other symptoms in a condition that resembles roseola infantum. While HHV-7 is less likely to reactivate than some other human herpesviruses, it can reactivate in people with weakened immune systems, especially among people who have recently received organ transplants. Infections caused by HHV-7 are not generally very serious in people with healthy immune systems
HHV-8: Kaposi’s Sarcoma Herpesvirus
HHV-8, also known as KSHV, or Kaposi’s Sarcoma Herpesvirus, is not as common as the other strains of HHV discussed here. In the U.S., it is estimated that less than five percent of the total population carry HHV-8, with most cases concentrated among men who have sex with men and intravenous drug users. However, HHV-8 is much more common in sub-Saharan Africa, where it is not necessarily associated with drug use or men who have sex with men. In sub-Saharan Africa, most people with HHV-8 contract the virus during childhood, with some regions reporting prevalences of between 30 and 80 percent. HHV-8 is spread by contact with respiratory droplets and nasal secretions, and may be sexually transmitted.
- Swollen lymph glands
Immunosuppressed people who contract HHV-8 may experience the symptoms listed above, as well as enlarged lymph glands, enlarged spleen and a blood disorder known as pancytopenia. This last is a condition in which levels of red blood cells, white blood cells and platelets all drop, leading to fatigue, anemia, bruising and a weakened immune system.
In some cases, they may also experience bone marrow failure and/or develop Kaposi’s sarcoma. HHV-8 has also been linked to:
- Primary effusion lymphoma, a type of lymphoma that develops in body cavities
- Multicentric Castleman disease, a condition in which non-cancerous tumors develop in one or more lymph nodes
In most cases, the condition most often associated with HHV-8 infection is Kaposi’s sarcoma.
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