HUMAN HERPESVIRUS 6
HHV-6 has a very high prevalence (close to 100% of the world’s population has been exposed). It is transmitted mainly by saliva. Transmission occurs usually within the first two years of life; primary infection is often associated with a febrile condition and sometimes with the onset of roseola (exanthem subitum). Two variants of the virus are known, HHV-6A and HHV-6B. HHV-6 is mainly lymphotropic, infecting a broad range of immune cells including T cells, monocytes, NK cells; however the virus can also infect many other tissues such as brain or liver.
HHV-6 has immunomodulatory effects, including suppression of T-cell proliferation and alteration of cytokine production. This immunosuppression may favor the development or progression of other viral infections such as CMV, EBV or HIV.
Several studies have reported a possible link between HHV-6 and multiple sclerosis (MS). Expression of HHV-6 proteins is observed at the site of MS lesions; cell-free HHV-6 DNA has been detected in the serum of MS patients. Reactivation of HHV-6 is also suspected to contribute to the pathogenesis of CFS.
HUMAN HERPESVIRUS 7
HHV-7 is closely related to HHV-6. Primary infection with HHV-7 usually occurs later in childhood than HHV-6 infection; it can also cause exanthem subitum. HHV-7 may have a narrower tropism than HHV-6: the virus efficiently infects and replicates in CD4+ cells; it can be found in brain tissue but at a lower frequency than HHV-6.
It has been suggested that HHV-7 could reactivate HHV-6 from latency. Increased prevalence has been reported in people with autoimmune disease.
CMV is transmitted through close personal contact (saliva, blood, breast milk, semen…). 20% of children are already infected before puberty; infection is then common during adolescence. Finally 40 to 100% of the general population will show evidence of prior exposure.
Primary CMV infections in newborns can lead to severe complications, but in older children and adults, primary infection is usually asymptomatic. After infection CMV remains latent in the host and can be reactivated when the immune system is severely impaired. Reactivation of the virus can target the central nervous system (acute encephalitis), damage the retina or have dermatologic manifestations (rash, ulcerative lesions). A pathogenic role of CMV in irritable bowel disease is suspected.
EBV (HHV-4) infects more than 90% of the world’s adult population. It is transmitted by salivary contact; the virus first replicates in the epithelium of the oropharynx before infecting B lymphocytes where it will persist for life in a latent state. Primary infection typically occurs within the first years of life and is generally asymptomatic. In developed countries however, primary infection is sometimes delayed until late adolescence, and may then result in mononucleosis.
In most individuals persistence of the virus has no consequences; in some people however EBV is associated with the development of cancer. EBV infections were first found to be associated with Burkitt’s lymphoma (a common cancer affecting children in certain regions of Africa) and have been implicated in Hodgkin’s disease, non-Hodgkin’s lymphoma, and nasopharyngeal carcinoma (in specific Asian regions).In addition to cancer, EBV has been linked to various immune diseases. By infecting T and NK cells, EBV can cause hemophagocytic syndrome (EBV-AHS).
There is evidence that multiple sclerosis may sometimes occur as a consequence of an EBV infection. Serum antibodies to EBV antigens are found in a subset of CFS patients; since EBV infections can lead to infectious mononucleosis, whose acute symptoms are similar to those of CFS, EBV was once proposed to be the primary causative agent.