Human Herpesvirus 6: An Emerging Pathogen

Abstract

Infections with human herpesvirus 6 (HHV-6), a ß-herpesvirus of which two variant groups (A and B) are recognized, is very common, approaching 100% in seroprevalence. Primary infection with HHV-6B causes roseola infantum or exanthem subitum, a common childhood disease that resolves spontaneously. After primary infection, the virus replicates in the salivary glands and is shed in saliva, the recognized route of transmission for variant B strains; it remains latent in lymphocytes and monocytes and persists at low levels in cells and tissues. Not usually associated with disease in the immunocompetent, HHV-6 infection is a major cause of opportunistic viral infections in the immunosuppressed, typically AIDS patients and transplant recipients, in whom HHV-6 infection/reactivation may culminate in rejection of transplanted organs and death. Other opportunistic viruses, human cytomegalovirus and HHV-7, also infect or reactivate in persons at risk. Another disease whose pathogenesis may be correlated with HHV-6 is multiple sclerosis. Data in favor of and against the correlation are discussed.

Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

“…Our present finding that all four CD46 isoforms function effectively as HHV-6 receptors suggests that differential expression of the various isoforms on different cell and tissue types is unlikely to be a major determinant of HHV-6 tropism. Also of potential significance for pathogenesis is that CD46 engagement by HHV-6 causes down-modulation of IL-12 secretion by activated blood-derived macrophages, 3 as has been shown previously for MV in these same cells (39) and in vivo (40). Thus, this potentially immunosuppressive effect can be induced by distinct viruses that interact with different regions of CD46.…”

“…The present findings concerning CD46 domain usage can be considered in terms of various aspects of HHV-6 pathogenesis. CD4 ϩ T lymphocytes have generally been considered to be the major targets for HHV-6 replication in vivo (1)(2)(3). However, recent studies have emphasized the importance of monocyte/ macrophages during the acute stage of infection (38); such cells could contribute to the latency of HHV-6, as well as to the transport of the virus across the blood-brain barrier.…”

Virally encoded 7TM receptors

“…Early in vitro studies revealed that HHV6 DNA fragments ± one of which included the viral chemokine receptor U12 ± could transform cells and induce tumours in nude mice. However, these studies had some major caveats (reviewed in Campadelli-Fiume et al, 1999), so the present view is to look at the virus as an innocent bystander (Luppi and Torelli, 1996). Interestingly, cases of lymphomas and acute lymphoblastic leukaemia have been reported, where the viral genome has been integrated into host chromosomes, but the biological signi®cance of these observations still remains elusive (Luppi et al, 1993;Daibata et al, 1998Daibata et al, , 1999.…”

Antibody status to HHV-6 in children with leukaemia

“…5,22,23 Both A and B subgroups of HHV-6 virus have a primary tropism for CD4 + T lymphocytes. There is evidence, that HHV-6 can directly target natural killer cells, thereby suppressing the natural anti-viral immunity of the host.…”