Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Abstract

SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus.

Extracellular vesicles: novel vehicles in herpesvirus infection

“…Markedly different from other HHVs, HHV-6 integrates its genomic DNA into the subtelomeric part of cell chromosomes in approximately 1% of the population (Agut et al, 2015). Evidence of its exosomal presence was presented in a study by Yasuko Mori et al The authors showed that cells that were infected with HHV-6 were larger than uninfected ones and contained MVBs in the late period of infection.…”

Human Herpesvirus 6B Downregulates Expression of Activating Ligands during Lytic Infection To Escape Elimination by Natural Killer Cells

“…A variety of clinical complications were found to be associated with HHV-6 infection, especially concerning immunocompromised patients, in whom it has the ability to cause severe morbidity and mortality (1,2). HHV-6 is subclassified into two distinct variants, HHV-6A and HHV-6B, which are considered independent viruses but share major genome sequence homologies and epidemiologies (3,4).…”

Герпесвірусний Гепатит 6-Го Типу У Дитини Раннього Віку

“…Первичная ВГЧ-6-инфекция встречается чаще у детей первых 3 лет жизни в двух основных кли-нических формах: розеола и лихорадка без сыпи [11][12][13]. Могут отмечаться фебрильные судороги, 29-36 % фебрильных судорог связано с ВГЧ-6, трансформируясь в дальнейшем в эпилепсию [11,14,15].…”