Target cells in vitro

The finding that both HHV-6 variants use the ubiquitous molecule CD46 as a membrane receptor is compatible with a broad cellular tropism. Productive infection, however, is limited to a small range of cells most likely by intracellular restriction factors acting beyond the viral entry step. Studies on the cellular tropism of HHV-6, and particularly of the A variant, have suggested that this virus is broadly 'immunotropic' as it infects several cells implicated in the generation of effective immune responses. Thereby, HHV-6 may affect, directly or indirectly, both the cellular and humoral arms of the immune system (see below). There is universal consensus that the primary target cells for HHV-6 infection both in vivo and in vitro are CD4+ T-Cells (Lusso et al., 1988; Takahashi et al., 1989). When activated mononuclear cells obtained from different sources (e.g. cord or peripheral blood, thymus, tonsils, lymph node) are exposed in vitro to HHV-6, the vast majority of the infected cells display the phenotype of activated CD4+ T-cells (CD2 + , CD4+, CD5 + , CD7 + , CD26 + , CD38 + , CD71+). In SCID-hu Thy/Liv mice, thymocytes at different maturation stage are productively infected (Gobbi et al., 1999). In studies performed using human lymphoid tissue blocks ex vivo (see below), both naive (CD45RA + 62L+) and memory T-cells were shown to be productively infected with HHV-6A (Grivel et al., 2003). However, there are some important differences in the in vitro cellular tropism of the two major viral subgroups (A and B). Besides the differential ability to infect human T- and B-cell lines (Table 1), HHV-6A efficiently infects different types of cytotoxic effectors, such as CD8+ T-cells (Lusso et al., 1991a,b), natural killer (NK) cells (Lusso et al., 1993), and y8 T-cells (Lusso et al., 1995). Because such cells are involved in the mechanisms of antiviral defense in vivo, this strategy may allow HHV-6 to counteract the protective immune surveillance of the host and thereby establish persistent infection. By contrast, HHV-6B seems to have a more restricted cellular tropism and, in particular, to infect rather inefficiently cytotoxic effector cells (Lusso et al., 1991a; Grivel et al., 2003).

Table 1

Tropism of HHV-6A and -6B for primary and immortalized lymphoid cells

Tropism of HHV-6A and -6B for primary and immortalized lymphoid cells

Table 1

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