The Human Herpes Viruses
Claire Watt Humans & Viruses 2008 Professor Robert Siegel Stanford University
"O'er ladies lips, who straight on kisses dream, Which oft the angry Mab with blisters plagues..." - William Shakespeare, "Romeo & Juliet"
The herpesviridae family, which contains more than 100 vertebrate viruses, is one of the oldest families of viruses known to infect humans. It has been described by scientists, poets, and wide variety of other individuals throughout the ages, from Shakespeare to Hippocrates. Thought to have been present in the earliest humans, herpesviruses have been isolated from individuals in every region of the world, including the most remote human populations, and are the cause of many of the most well known viral disease - from cold sores to chickenpox.
There are 8 herpesviruses known to infect humans:
Explore this site and the links provided for more information about the history, diseases, important facts, current research and more involving herpes viruses!
As early as the 500 BCE, herpesvirus infections were described by humans. Hippocrates himself described the effects of cutaneous herpesvirus infections, referencing the spreading lesions characteristic of many human herpesviruses.
The term "herpes," from the Greek root meaning "to creep," was first used to describe shingles, the clinical manifestation of Varicella-Zoster Virus (VZV) reactivation also known as herpes zoster.
In the 16th Century, Shakespeare also described the effects of herpesvirus infection in humans in “Romeo & Juliet.” In Mercutio's speech about Queen Mab, he wrote, "O'er ladies lips, who straight on kisses dream, which oft of the angry Mab with blisters plagues..." Shakespeare was talking about the characteristic lesions caused by Herpes Simplex Virus (HSV), more commonly known as cold sores or fever blisters (shown in the picture below).
Varicella, more commonly known as chickenpox, is a vesicular exanthem caused by infection with Varicella-Zoster Virus (VZV). Although chickenpox, like core sores and other lesions caused by HSV, has been documented for many centuries, it was often considered as indistinguishable from mild cases of smallpox. In the late 18th century, however, Heberden created detailed clinical descriptions to facilitate differentiation between cases of smallpox and chickenpox.
Although cold sores and other infectious lesions caused by Herpes Simplex Virus (HSV) had already been described, Vidal in 1893 was the first to propose that person-to-person transmission could cause the spread of cold sores caused by HSV.
In 1919, Lowenstein confirmed the hypothesis put forth by Vidal by experimentally illustrating the infective nature of HSV.
In the 1920s through the 1930s, research on HSV flourished, and the natural history of herpesvirus infections was described in much more detail for the first time. During this era, virologists first identified that HSV could infect more than just cutaneous tissue, and HSV infections of the central nervous system, such as herpes encephalitis, were examined in detail.
In the 1930s, extensive research was conducted on the host immune response to herpesvirus infections. These studies were the first to describe the properties of latency and reactivation that allow herpesvirus to persist in human hosts throughout their lifetime, causing sporadic reactivations of symptoms. Varicella-Zoster Virus (VZV) for example, causes the ubiquitous childhood disease, chickenpox. It then establishes a latent infection for decades, but can reactivate more than a century later to cause herpes zoster, or shingles (pictured above).
In the 1940s, ongoing research was conducted describing the variety of clinical manifestations of herpesvirus infections. This research led to the first descriptions of neonatal herpes cases.
In 1952, Weller and Stoddard proved von Bokay's hypothesis that varicella (chickenpox) and zoster (shingles) were caused by the same etiological agent. Weller and Stoddard isolated virus from both chickenpox and shingles lesions, and proved that the viruses were identical.
Although neonatal herpes had already been described in depth, the mechanism of vertical transmission in neonatal HSV infections wasn't identified until the late 1960s. It was only then that maternal genital HSV infections were causally associated with neonatal herpes.
Also known as human herpesvirus 4 (HHV-4), Epstein-Barr virus (EBV) was first isolated by Michael Epstein and Yvonne Barr in 1964. EBV often causes asymptomatic infections; it is also the leading cause of infectious mononucleosis, a syndrome which can also be caused by other herpesviruses such as cytomegalovirus (CMV).
Although Epstein-Barr virus (EBV) had first been isolated 4 years previously, Gertrude and Werner Henle were first to identify the newly discovered virus as a member of the herpesvirus family in 1968.
In 1988, von Bokay hypothesized for the first time that chickenpox and herpes zoster, regarded at the time as completely separate clinical phenomena, were in fact caused by the same infectious agent. This hypothesis was later confirmed by Weller and Stoddard, who isolated varicella-zoster virus (VZV) from both chickpox and herpes zoster lesions, confirming that the two manifestations are indeed both caused by VZV.
Acyclovir, an nucleoside analogue that is an extremely effective antiviral drug, was developed by pharmacologist Gertrube Elion, who won the Nobel Prize in Medicine in 1988. Commonly heralded for its widespread antiviral action and low toxicity, acyclovir is a very effective inhibitor of viral DNA polymerase, and is used as a first-line antiviral drug to treat HSV type 1 and type 2, Varicella-Zoster, and, to a lesser extent, Epstein-Barr virus and cytomegalovirus.
In 1995, the first vaccine effective against preventing any member of the herpesviridae family was licensed in the US. This vaccine, known by the brand name Varivax, is a live varicella vaccine developed by Merck to prevent chickenpox. It is currently included in routine vaccinations, and is also available in hetero-, multivalent vaccine combinations, such as the measles, mumps, rubella, and varicella tetravalent vaccine.
A second vaccine against Varicella-Zoster Virus (VZV), this one for the prevention of herpes zoster (or shingles), was developed by Merck and licensed in 2006. It is recommended for use in individuals older than 60 years old.
Created by Claire Watt, for Professor Robert Siegel's Humans and Viruses course
Stanford University, 2008