Instruct: Given a question, retrieve relevant documents that can help answer the question.
Query: How is human herpesvirus 6 spread?
Transmission is believed to occur most frequently through the shedding of viral particles into saliva. Both HHV-6B and HHV-7 are found in human saliva, the former being at a lower frequency. Studies report varying rates of prevalence of HHV-6 in saliva (between 3–90%),[13] and have also described the salivary glands as an in vivo reservoir for HHV-6. The virus infects the salivary glands, establishes latency, and periodically reactivates to spread infection to other hosts.[23]
A variety of tests are used in the detection HHV-6, some of which do not differentiate the two species.[7]
Nine herpesvirus types are known to infect humans: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2, also known as HHV1 and HHV2), varicella-zoster virus (VZV, which may also be called by its ICTV name, HHV-3), Epstein–Barr virus (EBV or HHV-4), human cytomegalovirus (HCMV or HHV-5), human herpesvirus 6A and 6B (HHV-6A and HHV-6B), human herpesvirus 7 (HHV-7), and Kaposi's sarcoma-associated herpesvirus (KSHV, also known as HHV-8).[10] In total, more than 130 herpesviruses are known,[11] some of them from mammals, birds, fish, reptiles, amphibians, and mollusks.[10]
HHV-6 reactivation has also been implicated in the exacerbation of MS via a shift in Th lymphocyte subsets.[64]
The DRESS syndrome is a severe immunological drug reaction. It differs from other drug reactions in that it: a) is caused by a particular set of drugs; b) typically occurs after a delay of 2 to 8 weeks following intake of an offending drug; c) presents with a specific set of signs and symptoms (i.e. modest or extreme elevations in blood eosinophil and atypical lymphocyte counts; acute onset of a skin rash; lymphadenopathy; fever; neuralgia; and involvement of at least one internal organ such as the liver, lung, or heart; d) develops in individuals with particular genetic predispositions; and e) involves reactivation of latent viruses, most commonly human herpesvirus 6 or more rarely human herpes virus 5 (i.e. human cytomegalovirus), human herpesvirus 7, and human herpesvirus 4 (i.e. Epstein–Barr virus). These virus usually become dormant after infecting humans but under special circumstances, such as drug intake, are reactivated and may contribute to serious diseases such as the DRESS syndrome.
Caretta caretta herpesvirus Chelonid herpesvirus 1 Chelonid herpesvirus 2 Chelonid herpesvirus 3 Chelonid herpesvirus 4 Chelonia mydas herpesvirus Coober herpesvirus Emydid herpesvirus 1 Emydid herpesvirus 2 Fibropapilloma associated herpes virus Gerrhosaurid herpesvirus 1 Gerrhosaurid herpesvirus 2 Gerrhosaurid herpesvirus 3 Glyptemis herpesvirus 1 Glyptemys herpesvirus 2 Iguanid herpesvirus 1 Iguanid herpesvirus 2 Loggerhead orocutaneous herpesvirus Lung-eye-trachea associated herpesvirus Pelomedusid herpesvirus 1 Red eared slider herpes virus Terrapene herpesvirus 1 Terrapene herpesvirus 2 Testudinid herpesvirus 1 Testudinid herpesvirus 2 Testudinid herpesvirus 3 Testudinid herpesvirus 4 Varanid herpesvirus 1 Subfamily Betaherpesvirinae Genus Proboscivirus Porcine herpesvirus 2 causes inclusion body rhinitis in swine. Subfamily Gammaherpesvirinae Phascolarctid gammaherpesvirus 1 Vombatid gammaherpesvirus 1 Genus Macavirus Genus Percavirus Genus Rhadinovirus Alcelaphine herpesvirus 1 causes bovine malignant catarrhal fever. Alcelaphine herpesvirus 2 causes an antelope and hartebeest version of MCF Ateline herpesvirus 2 Bovine herpesvirus 4 Cercopithecine herpesvirus 17 Equine herpesvirus 2 causes equine cytomegalovirus infection. Equine herpesvirus 5[29] Equine herpesvirus 7 Japanese macaque rhadinovirus[30] Leporid herpesvirus 1 Murid herpesvirus 4 Also known as Murine gammaherpesvirus-68 (MHV-68)
Family: Herpesviridae Subfamily: Alphaherpesvirinae Genus: Iltovirus Gallid herpesvirus 1 Psittacid herpesvirus 1 Genus: Mardivirus Anatid herpesvirus 1 Columbid herpesvirus 1 Gallid herpesvirus 2 Gallid herpesvirus 3 Meleagrid herpesvirus 1 Genus: Scutavirus Chelonid herpesvirus 5 Genus: Simplexvirus Ateline herpesvirus 1 Bovine herpesvirus 2 Cercopithecine herpesvirus 2 Human herpesvirus 1 Human herpesvirus 2 Leporid herpesvirus 4 Macacine herpesvirus 1 Macropodid herpesvirus 1 Macropodid herpesvirus 2 Papiine herpesvirus 2 Saimiriine herpesvirus 1 Genus: Unassigned Chelonid herpesvirus 6 Genus: Varicellovirus Bovine herpesvirus 1 Bovine herpesvirus 5 Bubaline herpesvirus 1 Canid herpesvirus 1 Caprine herpesvirus 1 Cercopithecine herpesvirus 9 Cervid herpesvirus 1 Cervid herpesvirus 2 Equid herpesvirus 1 Equid herpesvirus 3 Equid herpesvirus 4 Equid herpesvirus 8 Equid herpesvirus 9 Felid herpesvirus 1 Human herpesvirus 3 Phocid herpesvirus 1 Suid herpesvirus 1 Sub-Family: Betaherpesvirinae Genus: Cytomegalovirus Aotine herpesvirus 1 Cebine herpesvirus 1 Cercopithecine herpesvirus 5 Human herpesvirus 5 Macacine herpesvirus 3 Panine herpesvirus 2 Papiine herpesvirus 3 Saimiriine herpesvirus 4 Genus: Muromegalovirus Murid herpesvirus 1 Murid herpesvirus 2 Murid herpesvirus 8 Genus: Proboscivirus Elephantid herpesvirus 1 Genus: Roseolovirus Human herpesvirus 7 Human herpesvirus 6A Human herpesvirus 6B Genus: Unassigned Caviid herpesvirus 2 Suid herpesvirus 2 Tupaiid herpesvirus 1 Sub-Family: Gammaherpesvirinae Genus: Lymphocryptovirus Callitrichine herpesvirus 3 Cercopithecine herpesvirus 14 Gorilline herpesvirus 1 Human herpesvirus 4 Macacine herpesvirus 4 Panine herpesvirus 1 Papiine herpesvirus 1 Pongine herpesvirus 2 Genus: Macavirus Alcelaphine herpesvirus 1 Alcelaphine herpesvirus 2 Bovine herpesvirus 6 Caprine herpesvirus 2 Hippotragine herpesvirus 1 Ovine herpesvirus 2 Suid herpesvirus 3 Suid herpesvirus 4 Suid herpesvirus 5 Genus: Percavirus Equid herpesvirus 2 Equid herpesvirus 5 Mustelid herpesvirus 1 Genus: Rhadinovirus Ateline herpesvirus 2 Ateline herpesvirus 3 Bovine herpesvirus 4 Cricetid herpesvirus 2 Human herpesvirus 8 Macacine herpesvirus 5 Murid herpesvirus 4 Murid herpesvirus 7 Saimiriine herpesvirus 2 Genus: Unassigned Equid herpesvirus 7 Phocid herpesvirus 2 Saguinine herpesvirus 1
Human herpesvirus 6 lives primarily on humans and, while variants of the virus can cause mild to fatal illnesses, can live commensally on its host.[13] It has been demonstrated that HHV-6 fosters the progression of HIV-1 upon coinfection in T cells.[37] HHV-6 upregulates the expression of the primary HIV receptor CD4, thus expanding the range of HIV susceptible cells. Several studies also have shown that HHV-6 infection increases production of inflammatory cytokines that enhance in vitro expression of HIV-1, such as TNF-alpha,[38] IL-1 beta, and IL-8.[39] A more recent in vivo study shows HHV-6A coinfection to dramatically accelerate the progression from HIV to AIDS in pigtailed macaques.[40]
Human herpesvirus 6 (HHV-6) is the common collective name for human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B). These closely related viruses are two of the nine herpesviruses known to have humans as their primary host.[1]
Primary infection in adults tend to be more severe.[13]
Homologous recombination is the proposed mechanism whereby the DNA virus "human herpesvirus-6" integrates into human telomeres.
However, one group of researchers ultimately concluded that HHV-6 may not be involved in MTLE related to Mesial Temporal Sclerosis.[86]
Since moving to Cambridge, Minson's research has focused on animal viruses, particularly those of the herpesvirus family, including herpes simplex virus (HSV) and human cytomegalovirus. These large and complex enveloped DNA viruses commonly infect humans, causing a lifelong latent infection. Conditions associated with HSV include cold sores and genital herpes, and both HSV and cytomegalovirus can be life-threatening in people who are immunodeficient. Much of Minson's research has investigated herpesvirus replication and life cycle, and viral pathogenesis and the immune response. His work has contributed to understanding the processes by which HSV fuses with the cell membrane and acquires its envelope. As of 2013, his research focuses on herpesvirus entry, in particular how the viral membrane proteins cooperate to induce fusion, as well as assembly, in particular of the viral membrane proteins.
Roseola is an infectious disease caused by certain types of virus. Most infections occur before the age of three. Symptoms vary from absent to the classic presentation of a fever of rapid onset followed by a rash. The fever generally lasts for three to five days. The rash is generally pink and lasts for less than three days. Complications may include febrile seizures, with serious complications being rare.
It is caused by either "human herpesvirus 6" (HHV-6) or "human herpesvirus 7" (HHV-7). Spread is usually through the saliva of those who are otherwise healthy. However, it may also spread from the mother to baby during pregnancy. Diagnosis is typically based on symptoms but can be confirmed with blood tests. Low numbers of white blood cells may also be present.
Treatment includes sufficient fluids and medications to treat the fever. Nearly all people are infected at some point in time. Males and females are affected equally often. The disease was first described in 1910 while the causal virus was determined in 1988. The disease may reactivate in those with a weakened immune system and may result in significant health problems.
The salivary glands have been described as an in vivo reservoir for HHV-6 infection.[23]
Enquist's laboratory focuses on understanding the molecular mechanisms by which neuroinvasive alpha-herpesviruses spread in the mammalian nervous system. His work employs imaging technology, cell biology, and viral genetics to reveal how virion components move inside and between neurons. Experiments are divided between two general areas to visualize how infection spreads from one neuron to another in vitro (dissociated neurons) and in vivo (living animals and tissues). His students have developed compartmented neuronal cultures to establish separate fluid environments for neuronal axons and the soma from which they emanate. These compartmented neuronal cultures are used for in vitro study of directional infection of neurons by alpha herpesviruses. Students also have constructed a variety of herpesvirus mutants that define mechanisms of neuronal spread and provide useful tools for tracing neuronal circuitry in living animals and uncovering mechanisms of alpha-herpesvirus pathogenesis. Dr. Enquist has published 293 articles or books and is an inventor on four US patents.
Subfamily Alphaherpesvirinae Genus Simplexvirus Ateline herpesvirus 1, spider monkey herpesvirus. Bovine herpesvirus 2 causes bovine mammillitis and pseudo-lumpyskin disease. Cercopithecine herpesvirus 1, also known as Herpes B virus, causes a herpes simplex-like disease in macaques, usually fatal if symptomatic and untreated in humans. Fruit bat alphaherpesvirus 1 Leporid herpesvirus 4 Macacine herpesvirus 1 Macropodid herpesvirus 2 Papiine herpesvirus 2 Genus Varicellovirus Bovine herpesvirus 1 causes infectious bovine rhinotracheitis, vaginitis, balanoposthitis, and abortion in cattle. Bovine herpesvirus 5 causes encephalitis in cattle. Bubaline herpesvirus 1 Caprine herpesvirus 1 causes conjunctivitis and respiratory disease in goats. Canine herpesvirus 1 causes a severe hemorrhagic disease in puppies. Cercopithecine herpesvirus 9 Cervid herpesvirus 1 Cervid herpesvirus 2 Elk herpesvirus 1 Equine herpesvirus 1 causes respiratory disease, neurological disease/paralysis, and spontaneous abortion in horses. Equine herpesvirus 3 causes coital exanthema in horses. Equine herpesvirus 4 causes rhinopneumonitis in horses. Equine herpesvirus 8 Equine herpesvirus 9 Feline herpesvirus 1 causes feline viral rhinotracheitis and keratitis in cats. Suid herpesvirus 1 causes Aujeszky's disease, also called pseudorabies. Genus Mardivirus Anatid herpesvirus 1 Columbiform herpesvirus 1 Gallid herpesvirus 2 causes Marek's disease. Gallid herpesvirus 3 (GaHV-3 or MDV-2) Meleagrid herpesvirus 1 (HVT) Peacock herpesvirus 1 Genus Iltovirus Gallid herpesvirus 1 causes infectious laryngotracheitis in birds. Psittacid herpesvirus 1 causes Pacheco's disease in birds.
These were believed to have occurred as a result of a reactivation, as anti-HHV-6 IgM antibody levels were low.[83]
Human cytomegalovirus (HCMV, HHV-5) "seems to have a large impact on immune parameters in later life and may contribute to increased morbidity and eventual mortality." Human herpesvirus 6A (HHV-6A) has been described as more neurovirulent, and as such is more frequently found in patients with neuroinflammatory diseases such as multiple sclerosis. Both human herpesvirus 6B (HHV-6B) and human herpesvirus 7 (HHV-7), as well as other viruses, can cause a skin condition in infants known as exanthema subitum, roseola infantum (rose rash of infants) or the sixth disease.
During the progression of the DRESS syndrome certain viruses which previously infected an individual and then became latent are reactivated and proliferate. Viruses known to do so include certain members of the Herpesviridae family of Herpes viruses viz., Epstein-Barr virus, human herpesvirus 6, human herpesvirus 7, and cytomegalovirus. Individuals suffering the DRESS syndrome may exhibit sequential reactivation of these four virus, typically in the order just given. Reactivation of these viruses is associated with sequential flare-ups in symptoms, a prolonged course, and increased disease severity which includes significant organ involvement and the development of certain autoimmune diseases viz., systemic lupus erythematosus, autoimmune thyroiditis, and type 1 diabetes mellitus. While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in the pathogenesis of the DRESS syndrome, studies to date have not clearly determined if they are a cause or merely a consequence of T cell-mediated tissue injury. Rare case reports have associated the SJS/TEN spectrum of SCARs with reactivation of human herpesvirus 6; reactivation of cytomegalovirus has also been proposed to be associated with AGEP although a large study failed to observe the latter association. In all cases, the relationships of viral reactivation to the development and severity of any SCARs disorder is uncertain and requires further study.
Researchers[30] have shown that T cells are highly infectable by HHV-6.
Roseola is caused by two human herpesviruses, "human herpesvirus 6" (HHV-6) and "human herpesvirus 7" (HHV-7), which are sometimes referred to collectively as Roseolovirus. There are two variants of HHV-6 (HHV-6a and HHV-6b) and studies in the US, Europe, Dubai and Japan have shown that exanthema subitum is caused by HHV-6b. This form of HHV-6 infects over 90% of infants by age 2.
Human herpesvirus 7 (HHV-7) is one of nine known members of the Herpesviridae family that infects humans. HHV-7 is a member of Betaherpesviridae, a subfamily of the Herpesviridae that also includes HHV-6 and "cytomegalovirus" (HHV-5 or HCMV). HHV-7 often acts together with HHV-6, and the viruses together are sometimes referred to by their genus, "Roseolovirus". HHV-7 was first isolated in 1990 from CD4+ T cells taken from peripheral blood lymphocytes.
The role of HHV-6 during pregnancy leading to inflammation in the amniotic cavity has been studied.[77]
In viruses, like Saimiriine herpesvirus 2 ("Herpesvirus saimiri") and Human herpesvirus 8 (HHV-8/Kaposi's sarcoma-associated herpesvirus) cyclin D homologues have acquired new functions in order to manipulate the host cell’s metabolism to the viruses’ benefit.
Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the cell cycle. Other than Rb, viral cyclin D-Cdk6 complex also targets p27, a Cdk inhibitor of cyclin E and A. 
In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21 and p16 which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D.