Herpes B Virus
Encyclopedia
Herpes Simian B virus is the endemic simplexvirus of macaque
monkeys. B virus is an alphaherpesvirus, which consists of a subset of herpesviruses that travel within hosts using the peripheral nerves. As such, this neurotropic virus
is not found in the blood.
In the natural host, the virus
exhibits pathogenesis
similar to that of herpes simplex virus
(HSV) in humans. Conversely, when humans are zoonotically infected with B virus, patients can present with severe central nervous system
disease, resulting in permanent neurological dysfunction or death. Severity of the disease increases for untreated patients, with a mortality rate
of approximately 80%. Early diagnosis and subsequent treatment are the linchpins of surviving the infection.
Linked with more than two dozen deaths since its discovery, B virus is the only identified nonhuman primate herpesvirus that displays severe pathogenicity in humans. The last identified case of human B virus infection occurred in 2008, with the last known fatality occurring when a worker at the Yerkes National Primate Research Center
was infected in 1997 after an eye splash occurred. Proper personal protective equipment
is essential when working with macaques, especially those who have tested positive for the virus. Bites, scratches and exposures to mucous membranes, including the eye, must be cleaned immediately. Samples from both the macaque and human should be sent for B virus diagnostic testing as recommended by the B Virus Working Group here: BVIRUS.pdf
As of 2002, there were 26 documented cases of human B virus infection, 16 of which led to death. At least 20 of the patients developed some degree of encephalitis.
In October of 2011, numerous wild animals were set free and escaped from a wild animal farm preserve in Zanesville, Ohio, near Columbus, when the owner committed suicide. All but one of the animals, a monkey, have either been shot or have been taken to the Columbus Zoo; however, the remaining monkey is believed to be among the general public somewhere, and is thought to be infected with the herpes B virus.
. Soon after, Brebner developed localized erythema
, followed by lymphangitis
, lymphadenitis and, ultimately, transverse myelitis
. Neurologic tissues obtained during Dr. Brebner’s autopsy revealed the presence of an ultrafilterable agent that appeared similar to HSV. This isolate was originally termed “W virus.”
Within a year of Brebner’s death, Dr. Albert Sabin
identified an unfilterable agent from the same tissue, which he later named B virus. Sabin further described the lethality of B virus by showing that infectivity was independent of the route of inoculation. Additionally, it was observed that B virus induced immunologic responses similar to HSV-1, as well as shared similarities to HVP-2 and Langur herpesvirus, two other nonhuman primate alphaherpesviruses.
By 1959, B virus was identified as the causative agent in 17 human cases, 12 of which resulted in death. Approximately 50 cases had been identified by 2002, although only 26 were well documented. The latest identified case of B virus occurred in 2008, per the National B Virus Resource Center in Atlanta, GA.
was fully sequenced in 2003 from an isolate found in a rhesus macaque. Like all herpesviruses, the B virus genome contains double-stranded DNA
and is approximately 157 kbp in length. Two unique regions (UL and US) are flanked by a pair of inverted repeats, two of which are found at the termini, with the other two internally located. This arrangement, which is identical in nature to HSV, results in four sequence-oriented isomers. Cytosine
and guanine
nucleotides represent 75% of the sequence.
Sequence analyses suggest that B virus and HSV types 1 and 2 most likely diverged from a common ancestor during the evolution of these pathogens. Each gene-encoded glycoprotein
, including gB, gC, gD, gE and gG, has approximately 50% homology with HSV, with a slightly higher predilection towards HSV-2 over HSV-1. Additionally, glycoprotein sequences have demonstrated that all cysteine residues are conserved, as are most glycosylation
sites.
Macaque
The macaques constitute a genus of Old World monkeys of the subfamily Cercopithecinae. - Description :Aside from humans , the macaques are the most widespread primate genus, ranging from Japan to Afghanistan and, in the case of the barbary macaque, to North Africa...
monkeys. B virus is an alphaherpesvirus, which consists of a subset of herpesviruses that travel within hosts using the peripheral nerves. As such, this neurotropic virus
Neurotropic virus
A neurotropic virus is a virus which is capable of infecting nerve cells, or which does so preferentially. Such viruses thereby largely evade the usual immune response—which acts only within the blood system.- Terminology :...
is not found in the blood.
In the natural host, the virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
exhibits pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
similar to that of herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
(HSV) in humans. Conversely, when humans are zoonotically infected with B virus, patients can present with severe central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
disease, resulting in permanent neurological dysfunction or death. Severity of the disease increases for untreated patients, with a mortality rate
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
of approximately 80%. Early diagnosis and subsequent treatment are the linchpins of surviving the infection.
Linked with more than two dozen deaths since its discovery, B virus is the only identified nonhuman primate herpesvirus that displays severe pathogenicity in humans. The last identified case of human B virus infection occurred in 2008, with the last known fatality occurring when a worker at the Yerkes National Primate Research Center
Yerkes National Primate Research Center
The Yerkes National Primate Research Center, originally established and located in Orange Park, Florida but was later relocated to Atlanta, Georgia at Emory University, is one of eight national primate research centers funded by the National Institutes of Health...
was infected in 1997 after an eye splash occurred. Proper personal protective equipment
Personal protective equipment
Personal protective equipment refers to protective clothing, helmets, goggles, or other garment or equipment designed to protect the wearer's body from injury by blunt impacts, electrical hazards, heat, chemicals, and infection, for job-related occupational safety and health purposes, and in...
is essential when working with macaques, especially those who have tested positive for the virus. Bites, scratches and exposures to mucous membranes, including the eye, must be cleaned immediately. Samples from both the macaque and human should be sent for B virus diagnostic testing as recommended by the B Virus Working Group here: BVIRUS.pdf
As of 2002, there were 26 documented cases of human B virus infection, 16 of which led to death. At least 20 of the patients developed some degree of encephalitis.
In October of 2011, numerous wild animals were set free and escaped from a wild animal farm preserve in Zanesville, Ohio, near Columbus, when the owner committed suicide. All but one of the animals, a monkey, have either been shot or have been taken to the Columbus Zoo; however, the remaining monkey is believed to be among the general public somewhere, and is thought to be infected with the herpes B virus.
History
Herpes B virus was first identified in 1932 following the death of Dr. William Brebner, a young physician who was bitten by a monkey while researching the virus that causes poliomyelitisPoliomyelitis
Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the fecal-oral route...
. Soon after, Brebner developed localized erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
, followed by lymphangitis
Lymphangitis
Lymphangitis is an inflammation of the lymphatic channels that occurs as a result of infection at a site distal to the channel. The most common cause of lymphangitis in humans is Streptococcus pyogenes...
, lymphadenitis and, ultimately, transverse myelitis
Transverse myelitis
Transverse myelitis is a neurological disorder caused by an inflammatory process of the spinal cord, and can cause axonal demyelination. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation...
. Neurologic tissues obtained during Dr. Brebner’s autopsy revealed the presence of an ultrafilterable agent that appeared similar to HSV. This isolate was originally termed “W virus.”
Within a year of Brebner’s death, Dr. Albert Sabin
Albert Sabin
Albert Bruce Sabin was an American medical researcher best known for having developed an oral polio vaccine.-Life:...
identified an unfilterable agent from the same tissue, which he later named B virus. Sabin further described the lethality of B virus by showing that infectivity was independent of the route of inoculation. Additionally, it was observed that B virus induced immunologic responses similar to HSV-1, as well as shared similarities to HVP-2 and Langur herpesvirus, two other nonhuman primate alphaherpesviruses.
By 1959, B virus was identified as the causative agent in 17 human cases, 12 of which resulted in death. Approximately 50 cases had been identified by 2002, although only 26 were well documented. The latest identified case of B virus occurred in 2008, per the National B Virus Resource Center in Atlanta, GA.
Viral Genome
The B virus genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
was fully sequenced in 2003 from an isolate found in a rhesus macaque. Like all herpesviruses, the B virus genome contains double-stranded DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and is approximately 157 kbp in length. Two unique regions (UL and US) are flanked by a pair of inverted repeats, two of which are found at the termini, with the other two internally located. This arrangement, which is identical in nature to HSV, results in four sequence-oriented isomers. Cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
and guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
nucleotides represent 75% of the sequence.
Sequence analyses suggest that B virus and HSV types 1 and 2 most likely diverged from a common ancestor during the evolution of these pathogens. Each gene-encoded glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
, including gB, gC, gD, gE and gG, has approximately 50% homology with HSV, with a slightly higher predilection towards HSV-2 over HSV-1. Additionally, glycoprotein sequences have demonstrated that all cysteine residues are conserved, as are most glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
sites.