What are the causes of Human Herpesvirus 6 (HHV-6) infection?

From the Guidelines

Human Herpesvirus 6 (HHV-6) infection is primarily caused by person-to-person transmission through saliva and respiratory secretions, with most people acquiring the infection during early childhood, typically between 6 months and 2 years of age, when maternal antibodies wane 1. The virus spreads mainly through close contact with infected individuals, particularly through exposure to oral secretions. Some key points about HHV-6 transmission and infection include:

• Vertical transmission from mother to infant can also occur, either during pregnancy (transplacental), during delivery, or through breast milk, though this is less common 1.
• HHV-6 can also be transmitted through blood transfusions and organ transplantation in rare cases 1.
• The virus has two major variants: HHV-6A and HHV-6B, with HHV-6B being responsible for most primary infections in children 1.
• A unique feature of HHV-6 is its ability to integrate into human chromosomes and be inherited in approximately 1% of the population, known as chromosomally integrated HHV-6 (ciHHV-6) 1.
• After primary infection, HHV-6 establishes lifelong latency in the host, primarily in T lymphocytes, monocytes, and other cells, and can reactivate during periods of immunosuppression 1. The most recent and highest quality study suggests that approximately 90% of healthy children become infected with HHV-6 by 12 months of life, and virtually 100% acquire infection by 3 years of age 1.

From the Research

Causes of HHV-6 Infection

• HHV-6 infection is primarily caused by the transmission of the virus from mother to child, often through saliva, early in life 2.
• The virus can also be transmitted through airborne routes and can reactivate under conditions of immunosuppression, such as AIDS or organ transplantations 2.
• HHV-6 has cellular tropism for CD4+ lymphocytes, in which it replicates in vivo, and can cause various diseases, including exanthem subitum, lymphadenitis, and infectious mononucleosis-like disease 2.
• Reactivation of HHV-6 is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications 3.
• The risk of HHV-6 reactivation is higher in patients with acute leukemia, those who receive myeloablative conditioning regimens, and those who receive post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis 3.

Risk Factors for HHV-6 Infection

• Immunocompromised individuals, such as those with AIDS or those undergoing organ transplantation, are at higher risk of HHV-6 reactivation 2.
• Patients undergoing allo-HSCT, particularly those with acute leukemia, are at higher risk of HHV-6 reactivation 3.
• Non-cord blood transplant recipients are at higher risk of developing sequelae after receiving ganciclovir monotherapy for HHV-6 encephalitis 4.

Transmission and Prevention

• HHV-6 can be transmitted through airborne routes, as well as through contact with saliva or other bodily fluids 2.
• Preemptive therapy with antiviral agents, such as foscarnet, may be effective in preventing HHV-6 reactivation and reducing the risk of complications 3, 5.
• Combination therapy with foscarnet and ganciclovir may reduce sequelae, but not mortality, secondary to HHV-6 encephalitis 4.