Herpes B virus is an alpha herpesvirus that is particularly enzootic (endemic in animals) in the rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) members of the macaque genus, Macaca (as seen in the image below). Among the nonhuman-primate herpesviruses, only herpes B virus is clearly able to cause disease in humans. The disease, usually a devastating infection of the central nervous system, occurs in humans and some primates that are not common hosts for this virus.
The pathogen is an enveloped herpesvirus, approximately 160-180 nm in size, that is quite similar to the human herpes simplex virus (HSV). Herpes B contains double-stranded linear DNA and has a molecular weight of approximately 110 megadaltons (approximately 162 kilobase pairs). Analysis of the envelope glycoproteins suggests cross-reactivity of glycoproteins B and D between herpes B and HSV types 1 and 2. Herpes B virus demonstrates a broad host range in tissue culture, producing a lytic infection in cells of humans, nonhuman primates, small mammals, and many birds. [1, 2]
In 1934, the term herpes B was derived from the initials of the first human case, which was described in detail by Sabin and Wright. The case was that of a 29-year-old laboratory worker ("W.B.") who developed fatal meningoencephalitis and transverse myelitis following a bite on the hand from a seemingly healthy rhesus monkey.
Herpes B virus infects a broad range of mammalian and avian species, including New World monkeys, Old World monkeys, and humans. Most infected macaques are asymptomatic. When symptoms do occur, they are very similar to those caused by HSV. The most obvious manifestation of herpes B virus infection is fluid-filled vesicles on the back of the tongue, lips, and elsewhere in the mouth; occasionally, the vesicles appear on the skin. When the vesicles rupture, they often give rise to ulcers and fibronecrotic scabs, which may lead to secondary bacterial and fungal infections. Scabs typically heal within 7-14 days. Conjunctivitis of varying severity is another common symptom. In rare instances, systemic illness is associated with herpes B virus in macaques, including the occurrence of ulcerative lesions in the mouth, esophagus, and stomach and necrosis of the liver, spleen, and adrenal glands.
Members of the genus Macaca (>16 species) are natural hosts of herpes B virus, and almost all of these hosts naturally exist in Asia. Both wild and captive macaque populations generally exhibit high rates of herpes B virus infection, but most individuals exhibit few or no symptoms of infection. The strongest evidence for this pattern of high prevalence and mild infection comes from the rhesus, Japanese, and long-tailed (or cynomolgus) macaques, all of which are very closely related phylogenetically.
In captive populations of Japanese long-tailed and rhesus macaques, the prevalence of herpes B virus–induced antibodies is quite variable but may reach 100%. In wild and semi–free-ranging populations of long-tailed and rhesus macaques, seroprevalence rates (or prevalence of serum-detected herpes B virus–induced antibodies) typically exceed 70%.
Reports show that no herpes B virus exists in a population of long-tailed macaques introduced 400 years ago on the island of Mauritius. In all populations studied, the likelihood of infection increases dramatically with age. For example, in a study of semi–free-ranging macaques on the island of Cayo Santiago, Puerto Rico, 50% of 1-year-old macaques were infected, compared to 100% of adults. In a study of captive rhesus and Japanese macaques in Japan, the prevalence rates were 20% in 1-year-old monkeys and 60% in adults. Other macaque species readily acquire and transmit the virus, but whether these species serve as natural hosts is unclear.
Cercopithecine herpesvirus 1 (CHV-1), interestingly, is the formal name of the virus, which implies that all members of the primate family Cercopithecidae serve as natural hosts. Nevertheless, little evidence supports this theory for nonmacaque species of this taxon (eg, baboons, mangabeys, guenons, vervet monkeys); thus, CHV-1 may be a misnomer. Part of the difficulty in identifying taxonomic patterns is that many of the nonmacaque Cercopithecine species are natural carriers of closely related viruses (including the baboon herpesvirus SA8), which are serologically difficult to distinguish from herpes B.
After inoculation of herpes B virus in humans, dissemination to the central nervous system appears to occur neurally; however, herpes B virus can produce local infection in the skin at the inoculation site, with concomitant local and regional inflammatory changes. Indeed, lymph nodes draining the entry point can be histopathologically hemorrhagic and focally necrotic.
Introduction of the virus causes necrosis in the spinal cord with ascent to the brain. At least one case in which disease occurred years after exposure has been reported, suggesting that herpes B virus might be able to become latent in humans. Self-limited aseptic meningitis has been reported, but almost all cases produce substantial morbidity and mortality.
No evidence shows that the prevalence of herpes B virus in macaques varies by country; however, the pattern of human infection is remarkable. Of the roughly 45 well-documented cases of herpes B virus infection in humans, two thirds occurred in the United States and the others were reported in Canada and Great Britain. Interestingly, most of the well-documented human cases of herpes B virus infection occurred in the 1950s and 1960s, when large numbers of rhesus macaques were used in the production and testing of poliomyelitis vaccines. In the late 1980s, several cases in Pensacola, Florida and Kalamazoo, Michigan, refocused attention on herpes B virus, and several other cases have since been documented. This increased frequency coincides with an increased use of macaques in retroviral research.
The absence of reports of human herpes B virus infection from countries where macaques are prevalent and commonly interact with humans (eg, Japan) is striking. Whether the absence of these reports is due to the limited availability of herpes B virus diagnostic facilities (ie, actual cases not identified) or if some other factors are responsible (eg, different animal-handling procedures) is unclear. Concern exists that pet macaques (in addition to laboratory macaques) can spread the herpes B virus. Children are 3 times more likely to be bitten than adults. Macaques in 7 nonoccupational exposure incidents were found to be seropositive for herpes B virus in two thirds of cases.
Historically, human herpes B virus infection carries a case-fatality rate of approximately 70%, a rate similar to that of untreated HSV encephalitis.
As with HSV encephalitis, many survivors of herpes B virus infection have substantial residua.
The average age of persons who develop herpes B virus infection reflects the demographics of individuals involved with the care of primate hosts in research laboratories.
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