An Overview of The Herpes Virus

 The history of Herpes traces back to Ancient Greece. The Greeks coined the term Herpes which means “to creep/crawl” and they documented the description of the virus as sores appearing on the surface of people’s skin. The Roman Emperor Tiberius banned kissing in ceremonies to decrease the incidences of Herpes among people. It was until 1873, that Jean Baptiste Emile Vidal, a French doctor, confirmed that the virus could be transmitted from person to person. Characteristic wise, the Herpes virus is a double stranded DNA virus the size of 200nm that has an envelope and can only be transcribed. This envelope allows glycoproteins to carry out their functions such as bind to surface receptors and fusion. If the envelope is damaged, then the virus is not infectious. A capsid surrounds the core while the tegument, space between capsid and envelope, carries proteins to help initiate replication. Since it’s a bigger virus in comparison to other double stranded viruses such as Polyomaviruses and Papillomaviruses, the virus is able to produce its own polymerase. During replication, the glycoproteins attach to the cell receptors, envelope fuses in, which then allows the nucleocapsid and proteins to enter, as well as the DNA when the capsid releases touch from the nuclear membrane. Infection wise, the Herpes virus is latent and recurrent. The Herpes virus belongs to the order of Herpesvirales within the Herpesviridae family. There are a total of 103 species in the order (Louten, Jennifer). The Herpesviridae family is separated into subfamilies based on physiological and biological properties such as tropism, the variety of cells and tissues it can infect. The three subfamilies include: alphaherpesvirinae, betaherpesvirinae, and gammaherpesvirinae. In alphaherpesvirinae, the cell's short reproductive cycle and latency in neuron cells cause lacerations in the skin. As for Betaherpesvirinae, the cells experience long reproductive cycles, latentency occurs in immune cells such as lymphocytes and monocytes causing asymptomatic infections. Lastly, in Gammaherpesvirinae, there is latency in B cells leading to cancer. In total, there are 9 human herpesviruses known to infect humans. Examples of viruses for the subfamilies will be discussed in detail later on.

The herpes virus commonly known to the public is HSV1 and HSV2, alpha viruses. With a linear genome, the virus has no end telomeres therefore for protection and replication purposes the virus uses the hairpin structure that cleaves at the end to create more linear ends. Cytopathic effects that HSV have on animal cells include the clumping of chromatin in the nucleus. The virus is also known to induce alterations in the citric acid cycle by promoting the conversion of Aspartate into pyrimidines and purines creating more nucleic acids for its lifecycle. Studies support that about two thirds of the human population are infected with one or both types of herpes viruses. Crowded and unsanitary areas are most prone to have the highest rates of HSV infection. About 33% of kids raised in a low-income household arw more prone to HSV-1 than children from middle income households. In addition, it’s more likely that a man will pass on the infection to their female partner than vice versa (Wertheim, Joel). Common symptoms displayed by patients include cold sores around the mouth/lip or clusters (HSV1) or fluid blisters in the gential area that rupture after time (HSV2). In HSV2, the area with the lesions corresponds to the side of the affected ganglion. Other less common herpes disorders include lesion in the fingers/thumbs, eye herpes, and herpes affected the central nervous system. Herpes whitlow, lesions in the fingers/thumbs, happens through self-inoculation. Herpes gladiatorum, lesions on the neck and arms and face, arises from close contact sports (WebMD). As for Herpes simplex keratitis, the cornea of the eye is infected. HSV1 can be transmitted through sharing objects such as utensils and toothbrushes or infected individuals. For oral herpes, the primary infection is asymptomatic, but it can be symptomatic if severe. For recurrent infection, HSV1 is classified as asymptomatic. Adults can experience pharyngitis, fever, and headaches. HSV2 is transmitted during sexual contact. The first outbreak is described as being the most painful. HSV2 follows the same cycle of primary and recurrent infection as HSV1.

The virus is not active all the time meaning the virus will be dormant in nerve cells until an eventful trigger. Events that can lead to the outburst of recurring symptoms include suppressed immune system, stress, fatigue, trauma, menstrual period, or an illness. Statistically in the United States alone, 50% of people display HSV1 (Herpes Simple Type 1) symptoms while 15% display HSV2 (Herpes Simple Type 2) symptoms (Luo, 2017). Approximately 1 in 8 people suffer from HSV2. In some patients, the symptoms present themselves months or years later after being exposed to the virus, but in others the symptoms begin to show after two days to 2 weeks. Patients experiencing such symptoms have been infected by having oral, vaginal or anal sex with an infected individual. The virus will enter either through the oral or genital mucosa and replicate in the squamous epithelium. So, for this to happen there needs to be abrasions in the labium minora and vagina for females or prepuce for males. This replication is carried onto the unmyelinated sensory neuron fibers which then retrograde into the cell body of the dorsal ganglion root neuron. These abrasions or cracks are access to surface receptors on skin cells and even Langherans cells leading to infection. Dendritic cells and epidermal keratinocytes express HSV receptors. Endocytosis is a way that epidermal keratinocytes are affected with HSV. A production of interferons and cytokines result from infecting epidermal keratinocytes and Langerhan cells. As stated before, HSV will enter the terminals of sensory neurons. Upon arrival the glycoproteins disassemble from the cell membrane due to cell membrane fusion. After primary infection, comes recurrent infection in the epithelial cells for a lifetime in anterograde manner. The virus can’t be transmitted through toilet seats, swimming pools or ouching silverware, towels, or bedding (WebMD). To decrease the chances of contracting the virus, have one partner who has tested negative for the virus, and use a latex condom during sexual intercourse. If a person is in a relationship with an infected individual, then the individual should be aware of the antiviral medications the person is on and avoid sexual intercourse when the partner exhibits Herpes symptoms. Up to the 1960s, herpes infections were left untreated, but then chemists discovered antivirals drugs that could stop the replication of DNA material inside the virus genome (Centers for Disease Control and Prevention). These DNA inhibitors could be used for herpes encephalitis, herpes keratitis, immune suppression by HIV, organ transplant, and for those undergoing radiation or chemotherapy. Ten years later, guanine and acyclovir were synthesized to better treat herpes in adults and newborns. Though there is no cure for the virus, it can be treated with antivirals such as Valtrex, Famvir, and Zovirax. As for genital sores, warm baths can alleviate symptoms. In addition, antivirals, the immune innate system has been shown to play a role in response to infection of HSV for example, IFN-alpha and beta and Toll-like receptors2 and 9. Science has not developed a successful vaccine against herpes. The vaccine needs to elicit an innate immune response and control the infection at the mucosa and dorsal ganglion level.

Women who are pregnant with genital herpes need to keep up with their pre-natal visits to the doctor because infection can lead to miscarriage or premature delivery. Herpes virus could be passed on to the unborn baby, but it’s more common for the baby to be infected when in contact with the vaginal blisters during the delivery. Babies can develop neonatal herpes and display skin, eye and mouth lesions. The virus’s potency can cause the death of the baby. Therefore, mothers should take anti-herpes medication in order to reduce the virus symptoms during delivery, but if the symptoms still arise then the doctor can perform a C-section to avoid cross contamination.

HSV1 and HSV2 are the most commonly known types of herpes viruses, but as stated before there are various subfamilies. In the alphaherpesvirinae subfamily belongs HHV3 which causes chickenpox and shingles. HHV3 is the only known herpesvirus with a vaccine. Before the vaccine was discovered in 1995, 4 million cases existed but that number went down to 35,000 cases a year (Fahey, Michele A.). The vaccine was administered to one-year old infants in a series of 2 doses. Adults who experienced chickenpox as children can receive the zoster vaccine, a strong dose of chickenpox vaccine, which decreases the chance of developing shingles by 50%. This virus is an airborne virus, but can also be transmitted through bodily fluids, saliva and mucous. During primary infection, the respiratory epithelial cells are first invaded, then the t-cells in the tonsils (Fahey, Michele A.). Circulating t-cells will infect the liver, sensory ganglia, and spleen. After two weeks of the virus replicating in the body, the infected t-cells will produce proteins that bind onto the receptors of skin cells which causes lesions. When a person is first infected with this virus, the virus presents itself as chickenpox and it’s highly contagious. Symptoms that patient experience range from flu-like symptoms, rash on head and chest, fluid filled blisters, and skin lesions. If the virus returns, it presents itself as shingles. Shingles is rare in young adults with a strong immune response but can be more common and painful in elderly patients. With shingles, the fluid filled vesicles restrict to a specific area where the affected nerves lie. The vesicles can be itchy and painful due to the sensory nerves involved but will dry and heal over time. Shingles is a recurrent infection therefore a person may experience several episodes of the virus yearly. Topical ointments can be used to reduce the itching and antivirals such as acyclovir, valacyclovir, and famciclovir can be taken to alleviate symptoms.

HHV4, Epstein-Barr Virus, belongs to Gammaherpesvirinae family, an asymptomatic virus causes most cases of mononucleosis “kissing” disease (Centers for Disease Control and Prevention). This virus can be transmitted through bodily fluids and fomites. Primary infection happens in the epithelial cells in mouth and then spreads to the pharynx. Once in the pharynx, the infection attacks the b-cells in the tonsils. Antibodies and cytotoxic t-cells come to invade the infection, but the virus can establish latency in memory b-cells for recurrent infection. Symptoms experienced include fatigue, fever, pharyngitis, swollen lymph nodes, and splenomegaly. Infected patients are advised to rest, take over the counter medication, and drink lots of fluids. Antibiotics are administered if infected with a secondary bacterial infection.

HHV5, human cytomegalovirus, in the Betaherpesvirinae subfamily, an asymptomatic virus is most commonly acquired during adolescence or childhood. Transmission of this virus occurs through bodily fluids, sexual contact, fomites, and blood transfusions. Infection occurs at the mucosal epithelium and progresses into monocytes, smooth muscle cells, and endothelial cells (Centers for Disease Control and Prevention). Latency of virus builds on myeloid progenitor cells within the bone marrow that can differentiate into monocytes. HHV5 can act as a trigger in immunocompromised patients with HIV or post-organ transplant patients. Neonates can be born with this disease and display symptoms such as low birth weight, premature birth, rash, seizures, and microcephaly (Centers for Disease Control and Prevention). There is no known treatment, but antivirals can be used to alleviate symptoms.

Human herpesviruses type 6A/B and 7 are related to the Roseolovirus genus under the Betaherpesvirinae subfamily. HHV-6A/B can infect macrophages, monocytes, dendritic and neural cells, and during latency remain in bone marrow stem cells. HHV6 can activate in patients who undergo organ transplant. HHV6B and HHV7 are known to cause Roseola in infants. Roseola, a pink rash is contagious even when not visibly present. HHV7 can causes seizures accompanied with feve. Coughing, sneezing, saliva, and fomites classify as methods of transmission. A high fever, fatigue, runny nose, and rash will last for a few days before clearing up (Mayo, Clinic Staff). The virus goes away on its own, but the doctor can recommend over the counter medications.

Lastly, HHV-8, Kaposi’s Sarcoma-Associated Herpesvirus, under the gamma subfamily, correlates with risk of cancer. This virus predominates in Africa and is highly concentrated in saliva in comparison to other bodily fluids. Kaposi’s sarcoma displays itself in HIV infected individuals (American Cancer Society). The lesions appear in various areas of the body at the same time and can spread throughout the body. Purple benign tumors appear under the skin, nose, throat, lymph nodes, and other organs. Kaposi’s sarcoma can affect AIDS and HIV individuals at the visceral level, for example infection in the liver or lungs. Complications in the organs can be life threatening, but can be treated with radiation and chemotherapy, surgery, antivirals, or topical ointments to name a few.