Herpesvirus 6 Infection 

  • Author: Ruchir Agrawal, MD; Chief Editor: Russell W Steele, MD   more...
 
Updated: Mar 21, 2012
 

Background

After the discovery of human immunodeficiency virus (HIV) 1, HIV 2, and human T-cell lymphotrophic viruses (HTLV) I and II, an enhanced interest arose in the scientific community to isolate novel viruses from cultured lymphocytes of patients with HIV and other patients who are immunocompromised. The discovery of human herpesvirus 6 (HHV-6) is a result of this pursuit.

Human herpesvirus 6 was isolated from interleukin-2–stimulated peripheral leukocytes of HIV and lymphoproliferative disorders. Initially named human B-cell lymphotropic virus (HBLV), the virus later was designated human herpesvirus 6. Later, several strains of human herpesvirus 6 were isolated from the lymphocytes of children with exanthem subitum and patients with chronic fatigue syndrome and from the saliva of patients with HIV and healthy individuals. Human herpesvirus 6 is now recognized to have an extremely widespread distribution.

Like other herpesviruses, human herpesvirus 6 causes an initial infection, a life-long latency, and a clinical reactivation, especially in hosts who are immunocompromised.[1] Human herpesvirus 6 may be involved in the pathogenesis of multiple sclerosis; however, further studies are required to establish this association.[2]

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Pathophysiology

The infectious agent in roseola infantum/exanthem subitum was demonstrated to be present in blood by inoculating healthy infants with serum from ill infants, a procedure considered very dangerous by today's standards. Later, Yamashi et al isolated the virus from blood and demonstrated seroconversion to human herpesvirus 6 in infected infants.[3]

Human herpesvirus 6 belongs to the Betaherpesvirinae subfamily and to the Roseolovirus genus. Human herpesvirus 6 is divided further into variants A and B. The virion particle has a typical structure of a herpesvirus with a central core containing the viral DNA, a capsid, and a tegument layer that, in turn, is surrounded by a membrane. At the molecular level, human herpesvirus 6 encodes proteins similar to immune mediators in the chemokine family. The functional chemokine is encoded by an open reading frame U83; U12 and U51 encode the 7 transmembrane proteins analogous to the chemokine receptors. This molecular mimicry seems to help human herpesvirus 6 in immune invasion and long latency in the host cells.[4]

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Epidemiology

Frequency

United States

Seroprevalence is almost 100%. The virus is shed in and probably spread through saliva of asymptomatic seropositive children. Human herpesvirus 6B is the cause of most symptomatic infections of human herpesvirus 6.

International

Almost 100% in Europe, seroprevalence in the rest of the world also is close to 100% with certain exceptions, such as Morocco, which has 20% seroprevalence.

Mortality/Morbidity

Human herpesvirus 6 infections are mainly uncomplicated infections and have a self-limited course. Rarely, human herpesvirus 6 can be associated with fatal dissemination and death; 8 fatal cases have been reported. The causes of death were encephalitis, hepatitis,[5] sudden death in infancy, hemophagocytic lymphocytosis, and disseminated infections. In studies by Prezioso et al and Hoang et al, atypical monocyte infiltrate was found in multiple organs, including the brain, spleen, lungs, liver, heart, renal cortex, lymph nodes, and intestine.[6, 7]

Age

Possibly due to maternal antibody protection before this age, seropositivity is at its peak in infants aged 6-12 months. The virus is shed in and probably spread through saliva of asymptomatic seropositive children. Most children contract human herpesvirus 6 before they are aged 5 years.

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Contributor Information and Disclosures
Author

Ruchir Agrawal, MD  Chief, Allergy and Immunology, Aurora Sheboygan Clinic

Ruchir Agrawal, MD, is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Leonard R Krilov, MD  Chief of Pediatric Infectious Diseases and International Adoption, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital

Leonard R Krilov, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Medimmune Grant/research funds Cliinical trials; Medimmune Honoraria Speaking and teaching; Medimmune Consulting fee Consulting

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Larry I Lutwick, MD  Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Robert W Tolan Jr, MD  Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility

Disclosure: Novartis Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD  Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Sue Jue, MD, to the development and writing of this article.

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A 9-month-old infant boy presented with a 1-day history of high-grade fever and irritability. In the emergency department, the patient had a septic workup including lumbar puncture (adhesive bandage) with normal cerebrospinal fluid analysis results. He was admitted to the hospital.
A 9-month-old infant boy presented with a 1-day history of high-grade fever and irritability. In the emergency department, the patient had a septic workup including lumbar puncture with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on the third day of hospitalization. Within a few hours, an erythematous, pink papular (roseola), nonpruritic rash appeared, mainly on the trunk.
A 9-month-old infant boy presented with a 1-day history of high-grade fever and irritability. In the emergency department, the patient had septic workup including lumbar puncture with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on the third day of hospitalization. Within a few hours, an erythematous, pink papular (roseola), nonpruritic rash appeared mainly on the trunk. Patient was playful after supportive therapy. Antibiotics discontinued after 2 days of negative culture. Rash is distributed mainly over the trunk.
 
 
 
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