Host cell interactions of human adenovirus serotypes belonging to subgroups B (adenovirus type 3 [Ad3] and Ad7) and C (Ad2 and Ad5) were comparatively analyzed at three levels: (i) binding of virus particles with host cell receptors; (ii) cointernalization of macromolecules with adenovirions; and (iii) adenovirus-induced cytoskeletal alterations. The association constants with human cell receptors were found to be similar for Ad2 and Ad3 (8 x 109 to 9 x 109 M-'), and the number of receptor sites per cell ranged from 5,000 (Ad2) to 7,000 (Ad3). Affinity blottings, competition experiments, and immunofluorescence stainings suggested that the receptor sites for adenovirus were distinct for members of subgroups B and C. Adenovirions increased the permeability of cells to macromolecules. We showed that this global effect could be divided into two distinct events: (i) cointernalization of macromolecules and virions into endocytotic vesicles, a phenomenon that occurred in a serotype-independent way, and (ii) release of macromolecules into the cytoplasm upon adenovirus-induced lysis of endosomal membranes. The latter process was found to be type specific and to require unaltered and infectious virus particles of serotype 2 or 5. Perinuclear condensatiout of the vimentin ifiament network was observed at early stages of infection with Ad2 or Ad5 but not with Ad3, Ad7, and noninfectious particles of Ad2 or Ad5, obtained by heat inactivation of wild-type virions or with the H2 tsl mutant. This phenomenon appeared to be a cytological marker for cytoplasmic transit of infectious virions within adenovirus-infected cells. It could be experimentally dissociated from vimentin proteolysis, which was found to be serotype dependent, occurring only with members of subgroup C, regardless of the infectivity of the input virus.

The aim of this study was to investigate the following in a large population of French patients with chronic hepatitis C: the geographical distribution of hepatitis C virus (HCV) genotypes; the relationship between HCV genotypes and epidemiological characteristics; severity of the disease; and response to interferon (IFN) therapy. Data from 14 tertiary referral centres, corresponding to 1872 patients with chronic hepatitis C, were prospectively collected from 1989 to 1997. HCV genotyping was performed using the line probe assay (LiPA). HCV genotypes 1b, 3, 1a, 2, 4 and a mixed infection were found in 41%, 22%, 16%, 11%, 4% and 4% of our population, respectively. HCV genotype distribution was homogeneous, except for genotype 2 that was found more frequently in the southwest than in the other regions (21% vs 9.2%) (P=0.001). HCV distribution was associated with gender, age, and source and duration of infection. In multivariate analysis, these correlations were related to the source of infection, which was the only independent factor significantly associated with genotype (P=0.001). Genotype 1b was significantly more common in patients with cirrhosis, but in multivariate analysis cirrhosis was independently related to older age at exposure and longer duration of infection (P=0.001). A sustained response to IFN therapy was observed in 11% of patients infected with genotypes 1a or 1b vs 32% of those infected with genotypes 2 or 3 (P=0.001). This study shows that HCV genotype is mainly related to the source infection, but not to the intrinsic pathogenicity of HCV, and is a strong predictor of sustained response to therapy.