Human Herpesvirus 6 and Malignancy: A Review

Abstract

In order to determine the role of human herpesvirus 6 (HHV-6) in human disease, several confounding factors, including methods of detection, types of controls, and the ubiquitous nature of the virus, must be considered. This is particularly problematic in the case of cancer, in which rates of detection vary greatly among studies. To determine what part, if any, HHV-6 plays in oncogenesis, a review of the literature was performed. There is evidence that HHV-6 is present in certain types of cancer; however, detection of the virus within tumor cells is insufficient for assigning a direct role of HHV-6 in tumorigenesis. Findings supportive of a causal role for a virus in cancer include presence of the virus in a large proportion of cases, presence of the virus in most tumor cells, and virus-induced in-vitro cell transformation. HHV-6, if not directly oncogenic, may act as a contributory factor that indirectly enhances tumor cell growth, in some cases by cooperation with other viruses. Another possibility is that HHV-6 may merely be an opportunistic virus that thrives in the immunodeficient tumor microenvironment. Although many studies have been carried out, it is still premature to definitively implicate HHV-6 in several human cancers. In some instances, evidence suggests that HHV-6 may cooperate with other viruses, including EBV, HPV, and HHV-8, in the development of cancer, and HHV-6 may have a role in such conditions as nodular sclerosis Hodgkin lymphoma, gastrointestinal cancer, glial tumors, and oral cancers. However, further studies will be required to determine the exact contributions of HHV-6 to tumorigenesis.

The landscape of viral associations in human cancers

“…Still, we cannot rule out a substantial contribution of infected immune cells in pancreas and other tissues. Therefore, in line with current knowledge (reviewed in 16 ), we cannot confirm a link between roseolovirus and tumor development. Especially in matched non-malignant kidney samples, we detected higher roseolovirus positivity without an equally strong signal in the corresponding tumor samples.…”

The Presence of Human Herpesvirus 6 in the Brain in Health and Disease

“…While infection by HHV-6 is generally asymptomatic, HHV-6B is the etiological factor for exanthema subitum (roseola infantum) [27] which most often produces a non-life-threatening fever and skin rash. Other conditions have been associated to the acute infection or reactivation in immunocompromised individuals, including AIDS encephalopathy, several types of cancer, demyelinating diseases such as multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML), chronic fatigue syndrome, febrile seizures, multiple transplant complications, heart, lung and liver diseases, cognitive disfunction, epilepsy, and encephalitis [22,25,[28][29][30][31]. Recently, some studies have implicated the infection by HHV-6 in the pathogenesis of Alzheimer's disease (AD) [32,33].…”

Seropositivity for pathogens associated with chronic infections is a risk factor for all-cause mortality in the elderly: findings from the Memory and Morbidity in Augsburg Elderly (MEMO) Study

“…Cytomegalovirus (CMV), a herpes virus with seroprevalence levels between 31.8 and 77.6% in Western Europe (Lachmann et al 2018 ), has been shown to induce chronic antigenic stress (Pawelec and Gouttefangeas 2006 ), which accelerates immunosenescence (Aw et al 2007 ; Solana et al 2012 ). Other herpes viruses, like Epstein-Barr-Virus (EBV), the first identified human oncovirus (Epstein et al 1964 ), herpes simplex virus 1/2 (HSV-1/2) (Bergstrom et al 1990 ; Piacentini et al 2014 ) and human herpesvirus 6 (HHV-6) (Eliassen et al 2018 ) have been linked to the development of cancer and neurological diseases via immunostimulation. Bacterial pathogens, like Helicobacter pylori ( H. pylori ), the causative agent of gastric cancer and ulcer, and Borrelia burgdorferi sensu lato ( B. burgdorferi s.l. )…”