Molecular Biology

Important Herpes Virus Facts

The Human Herpes Viruses

New Findings

Further Information

Pathogen Cards



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"


Introduction to Herpesviruses 

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:

  1.  Herpes simplex virus I (genus: simplexvirus)
  2. Herpes simplex virus II (genus: simplexvirus)
  3. Varicella zoster virus (genus: varicellovirus)
  4. Epstein-Barr virus (genus: lymphocryptovirus)
  5. Cytomegalovirus (genus: cytomegalovirus)
  6. Human herpesvirus 6 (genus: roseolovirus)
  7. Human herpesvirus 7 (genus: roseolovirus)
  8. Human herpesvirus 8 (genus: rhadinovirus)

Explore this site and the links provided for more information about the history, diseases, important facts, current research and more involving herpes viruses!

Herpesviruses through the Centuries: a Timeline

 View the Herpesviridae Timeline!

500 BCE    

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. 

1920s - 1930s          

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.