The Effect of HDV Infection on the HBV Life Cycle

Since HDV is directly dependent on HBV for propagation, it can be transmitted concomitantly with HBV to an individual who has no history of prior HBV infection, this is referred to as a coinfection pattern - or it can be transmitted to an HBV chronic carrier, this is referred to as superinfection. Coinfections are often acute and self-limiting, and they result in a concomitant replication of both HBV and HDV, whereas superinfections cause severe acute and chronic type D hepatitis in 70% of cases. They also lead to the inhibition of HBV replication during the acute phase of HDV infection. This phenomenon has been describedinbothhumansand experimentallyinfectedchimpanzees, but it remains poorly understood (Chen et al. 1988; Sureau et al. 1989; Wu et al. 1991). It could result from a direct suppression of HBV replication exerted by the coexpressed HDV proteins, RNA or RNPs, or could be the consequence of an indirect interfering mechanism driven by inflammatory cytokines. The suppressive effect could also result from a hijacking of the envelope proteins by the RNPs in host cells when HDV RNA replication reaches maximum levels upon superinfection. Considering that an infected cell might contain as many as 6,000,000 copies of HDAg proteins and 60,000 copies of HDV RNA (Gudima et al. 2002), it is likely that the helper nucleocapsids be heavily outnumbered by the HDV RNPs in their access to the HBV budding machinery. In addition, faced with these huge amounts of RNPs ready for export, the budding system, though oversized for HBV, may reach saturation. There are at least seven HDV genotypes with various geographical distributions and a sequence divergence as high as 38% (Radjef et al. 2004; also the chapter by P. Deny, this volume), and eight HBV genotypes (designated A to H), also presenting different geographic distributions and a degree of sequence divergence greater than 8%. This raises the possibility for a broad range of HBV/HDV coinfection characteristics. A specific pathogenicity could result, in part, from the capacity of the HBV envelope proteins to export the RNP and/or to drive a progeny virion to uninfected hepatocytes. The most severe form of HBV/HDV coinfection has been recorded in South America where genotype III HDV was associated with genotype F HBV (Casey et al. 1996), the most divergent types in their respective family (Casey et al. 1993; Norder et al. 2004; Radjef et al. 2004). It would thus be interesting to characterize the envelope proteins of each HBV genotype for their ability to complement a given HDV genotype.

0 0

Post a comment