The classical presentation of primary<unk> b infection is as exanthema subitum (ES) or "roseola", featuring a high temperature followed by a rash. However, one study (1997) indicated that a rash is not a distinguishing feature of<unk>  infection, with rates similar to non-HHV-6 infections (10–20% of febrile children in both groups).<unk>  infections more frequently present with high temperatures (over 40C), at a rate of around two thirds compared to less than half in the non-HHV-6 patients. Similarly significant differences were seen in malaise, irritability, and tympanic membrane inflammation. Primary infection in adults tend to be more severe. Diagnosis for the virus, particularly<unk> B, is vital for the patient because of the infection's adverse effects. Symptoms that point to this infection, such as rashes, go unnoticed in patients that receive antibiotics because they can be misinterpreted as a side-effect of the medicine.<unk> B is known to be associated with the childhood disease roseola infantum, as well as other illnesses caused by the infection. These include hepatitis, febrile convulsions, and encephalitis. Children who suffer from exanthema subitum, caused by an<unk> B infection, experience fevers lasting 3 to 5 days; rashes on the torso, neck, and face; and sometimes febrile convulsions, however, the symptoms are not always present together. Primary infections in adults are rare since most occurrences are in children. When the infection does occur for the first time in an adult the symptoms can be severe. The virus periodically re-activates from its latent state, with<unk>  DNA being detectable in 20–25% of healthy adults in the United States. In the immunocompetent setting, these re-activations are often asymptomatic, but in immunosuppressed individuals there can be serious complications.<unk>  re-activation causes severe disease in transplant recipients and can lead to graft rejection, often in consort with other betaherpesviridae. Likewise in HIV/AIDS,<unk>  re-activations cause disseminated infections leading to end organ disease and death. Although up to 100% of the population are exposed (seropositive) to<unk> , most by 3 years of age, there are rare cases of primary infections in adults. In the United States, these have been linked more with<unk> a, which is thought to be more pathogenic and more neurotropic and has been linked to several central nervous system-related disorders.<unk>  has been reported in multiple sclerosis patients and has been implicated as a co-factor in several other diseases, including chronic fatigue syndrome, AIDS, and temporal lobe epilepsy. Multiple sclerosis Multiple sclerosis (MS) is an autoimmune and inflammatory disorder of the nervous system that results in demyelination of axons in the brain and spinal cord. The history of MS in the context of<unk>  began during 1995 when Peter Challoner, a scientist at PathoGenesis Corporation of Seattle, began looking for non-human genetic sequences in the brains of MS patients. He found an unusually high expression of<unk>  DNA within oligodendrocytes. He also noticed a higher concentration of infected cells in areas where demyelination had occurred. His research was likely the first published study to suggest a link between<unk>  and MS. Epidemiological data MS prevalence increases in populations as they are farther from the Equator. Incidence is three times higher in those born 42 degrees latitude north and above than in those born 37 degrees north and below. Individuals are also less likely to present with MS as an adult if their childhood was spent in a low incidence region. The possibility of a causative infectious agent in association with MS has been evaluated through the lens of these epidemiological findings. To explain the data above, two hypotheses were proposed. The first is known as the Poliomyelitis hypothesis and suggests that infection at a young age confers immunity but adult infection increases MS risk. The second is known as the Prevalence hypothesis, and suggests that MS is caused by a pathogen that is more common in regions with high rates of MS. This pathogen would be widespread and cause an asymptomatic (latent) infection in most individuals. Only rarely and years after the primary infection does this hypothetical agent cause the neurological symptoms of MS. A third hypothesis essentially combines these two and also suggests the involvement of multiple pathogens. The third may best apply to the epidemiological data. Possible viral involvement The Epstein–Barr virus (EBV) paradox is also noteworthy, as<unk>  has been reported to transactivate EBV. Individuals are at a 10-fold less risk of MS if they are seronegative for EBV. However, among individuals who are positive, those that acquire EBV infection later in life are at a 3-fold greater risk for MS. Research suggests that viral infections can be tied even closer to MS. EBV antibodies in healthy individuals remain constant, whereas antibody levels in individuals who later develop MS begin to increase and plateau between 20 and 30 years of age, regardless of age of onset. More specific to<unk> , researchers in 2004 discovered that the initial stages of MS are associated with high levels of the active virus. Soon thereafter, researchers discovered that levels of active<unk>  are also elevated during relapses/exacerbations of MS. Researchers have demonstrated that levels of<unk>  IgG1 and IgM antibodies are elevated in MS patients relative to controls. In fact, research published in 2014 found that increases in anti-HHV-6A/B IgG and IgM titers are predictive of MS relapse. Analysis of the epidemiological, serological, and immunological data above supports the association between an infectious agent and MS. However, the exact mechanism of a possible viral influence on the manifestation of MS is less clear. Although a few mechanisms have been suggested: molecular mimicry, phosphorylation pathways, and cytokines. Molecular mimicry The first study to specifically investigate<unk> -related demyelination appeared in the literature during 1996, when a previously healthy 19-month-old child developed acute encephalopathy. Levels of myelin basic protein were elevated in his cerebrospinal fluid, suggesting that demyelination was occurring. This link was almost forgotten, until four years later when an MS-related study was published showing an<unk>  prevalence of 90% among demyelinated brain tissues. In comparison, a mere 13% of disease-free brain tissues possessed the virus. The molecular mimicry hypothesis, in which T cells are essentially confusing an<unk>  viral protein with myelin basic protein, first appeared around this time. Early on in the development of this hypothesis (2002), Italian researchers used the<unk> a variant along with bovine myelin basic protein to generate cross-reactive T cell lines. These were compared to the T cells of individuals with MS as well as those of controls, and no significant difference was found between the two. Their early research suggested that molecular mimicry may not be a mechanism that is involved in MS. A few months later, researchers in the United States created a synthetic peptide with a sequence identical to that of an<unk>  peptide. They were able to show that T cells were activated by this peptide. These activated T cells also recognized and initiated an immune response against a synthetically created peptide sequence that is identical to part of human myelin basic protein. During their research, they found that the levels of these cross-reactive T cells are significantly elevated in MS patients. Their research concluded by suggesting that<unk>  may indeed be a causative agent for MS. Several similar studies followed. A study from October 2014 supported the role of long-term<unk>  infection with demyelination in progressive neurological diseases. Phosphorylation pathways Myelin basic protein (MBP) regularly exchanges phosphate groups with the environment, and its ability to do so has implications for proper myelin sheath integrity. More specifically, two threonine residues on MBP have been identified as the phosphorylation targets of glycogen synthase kinase and mitogen-activated protein kinase. Their action on MBP is said to aid in its ability to polymerize and bundle myelin. Phosphorylated MBP is also more resistant to several proteases. Among individuals with MS, these target threonines have been found to be phosphorylated less often. In fact,<unk>  produces a transmembrane protein, known as U24, that is also a phosphorylation target of the kinases mentioned previously. Our kinases act on an<unk>  protein due to a shared sequence of seven amino acids (MBP92–104=IVTPRTPPPSQGK; U241–13=MDPPRTPPPSYSE). As a result, essential post-translational modifications may not be occurring for MBPs in individuals with active<unk>  infections. * Multiple sclerosis – direct cell damage and altered cytokines<unk>  has been shown to infect olfactory ensheathing cells (OECs). OECs have been investigated thoroughly in relation to spinal cord injuries, amyotrophic lateral sclerosis, and other neurodegenerative diseases. Researchers suggest that these cells possess a unique ability to remyelinate injured neurons. Some of the genes expressed by<unk>  manipulate host levels of various cytokines (see section on gene products). For instance, infected cells have increased levels of interleukin-8, which is believed to induce MMP-9 repression. Elevated levels of MMP-9 have been found among individuals with MS.<unk>  reactivation has also been implicated in the exacerbation of MS via a shift in Th lymphocyte subsets. Chronic fatigue syndrome Chronic fatigue syndrome (CFS) is a debilitating illness, cause of which is unknown. Patients with CFS have abnormal neurological, immunological, and metabolic findings.
Human herpesvirus 6
Human betaherpesvirus 5
Human betaherpesvirus 7
Human T-lymphotropic virus 2
Human T-lymphotropic virus 1
Trichodysplasia spinulosa polyomavirus
Molluscum contagiosum virus
Epstein–Barr virus