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Human Herpesvirus Overview

Eight human herpesviruses (HHV) have been detected including herpes simplex (HSV), varicella zoster (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesviruses 6, 7, and 8. All are double-stranded DNA enveloped viruses and are further subclassified based on biologic behavior into alpha (HSV-1, 2, and VZV), beta (HHV-6, HHV-7, and CMV) and gamma herpesviruses (EBV and HHV-8).

A common characteristic of HHV is the establishment of latency following primary infections, with potential for subsequent reactivation. Primary infections are common in normal hosts; nearly all adults having been infected with HSV-1, VZV, EBV, HHV-6 and HHV-7. Alpha herpesviruses characteristically cause mucocutaneous infections in otherwise healthy individuals and then become latent in sensory neuroganglia. Beta herpesvirus infections become latent in mononuclear cells, while gamma herpesviruses become latent in lymphoid cells. Asymptomatic shedding of virus from oral mucosa is a characteristic feature of HSV, EBV, CMV, HHV-6, and HHV-7 and frequently results in person-to-person transmission. In contrast, VZV is transmitted only during primary infection (chickenpox) or reactivation (shingles) and is the only herpesvirus spread through airborne transmission. Reactivation most commonly occurs in immunocompromised individuals with impaired T-cell immunity. Both EBV and HHV-8 are associated with lymphoma and HHV-8 is associated with Kaposi’s sarcoma.

HHV-6 was initially recognized in patients with lymphoproliferative disorders. Most HHV-6 primary infections occur by age three and present as roseola infantum or sixth disease in immunocompetent children. Primary infections in adults are rare, and not associated with specific symptoms. The majority of HHV-6 disease in adults is due to reactivation of latent virus in immunocompromised individuals. Transplant patients, particularly those with hematopoietic stem cell transplants (HSCT) are at highest risk of developing pneumonitis, hepatitis, encephalitis, and bone marrow suppression.

A unique property of HHV-6 virus is the ability to integrate into the genome of approximately 1% of individuals. This endogenous virus can be detected by serologic and molecular PCR testing, making it difficult to interpret the clinical significance of positive diagnostic tests. A recent review of the BioFire FilmArray meningitis panel included 15 patients whose CSF tested positive for HHV-6. Only one patient, who underwent HSCT 3 weeks prior to testing, was believed to have true HHV-6 encephalitis. The remaining positive results were attributed to HHV-6 viral chromosomal integration or subclinical reactivation of latent virus and viral shedding.


Human Herpesvirus, Saint Luke’s Regional Laboratory Clinical Laboratory News, March 2019

Clinical Significance of Human Herpesvirus 6 Positivity on the FilmArray Meningitis/Encephalitis Panel, Clinical Infectious Disease 2018;67(7):1125-8

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