General cellular pathology of HHV6 infection

In vitro studies show the immediate effects of HHV-6 binding to cells, infection of susceptible cells and intracellular replication (see also Chapter 2: Ultrastructure of HHV-6). Susceptible cells (e.g. HSB2, cord blood cells) show upon exposure to HHV-6 blastic transformation with or without giant cell formation, intranuclear inclusions, eventual mitoses and production of viral particles with cellular degeneration and apoptosis (Fig. 1; Biberfeld et al., 1987; Kramarsky and Sander, 1992; Kirn et al., 1997). Blastic transformation with giant cells can occur in cells upon virus contacts even without subsequent internalization and replication of viral particles (Boehmer, 1987). Typical Reed-Sternberg-type giant cells were induced by HHV-6 in established Hodgkin cell cultures without spontaneous giant cells (L428, L540, L591, HDLM2, KMH2) and without subsequent viral replication in these cells (Fig. 1; Krueger et al., 1991, 1992, 1995). Internalization of virus particles and their replication initiate a number of cellular events, which are summarized in Table 1 and in Fig. 2. Cell membrane rigidification after HHV-6 infection and altered receptor availability, support superinfection by other viruses (Krueger et al., 1990; Schonnebeck et al., 1991; Lusso et al., 1995). NF-kB activation and other genomic effects down or upregulate other cell functions such as cell-cell cooperation and genomic transactivation of various genes (Lusso et al., 1995; Gies et al., 1998; Hasegawa et al., 2001; Arena et al., 2002), and oxidative burst and cell cycle control factors will induce cell degeneration and apoptosis (Deliconstantinos and Krueger, 1993; Kirn et al., 1997; Deliconstantinos et al., 1998).

The in vivo cellular effects of HHV-6 essentially correspond to those observed in vitro: stimulated cells may show blastic transformation and proliferate; productively infected cells may undergo degeneration and apoptosis. Prominent intranuclear inclusion bodies and giant cells are rarely seen in tissues, and when observed, these are highly suspicious for a dual infection with other herpesviruses, e.g. HHV-7.

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