ABSTRACT
Hepatitis E virus (HEV) genotype 3 produces zoonotic infection associated with the consumption of infected animals. HEV infections can become chronic in immunocompromised (IC) patients. The viral genome has three well defined open reading frames (ORF1, ORF2 and ORF3) within which various domains and functions have been described. This paper (i) describes a new method of complete sequencing of the HEV coding region through overlapping PCR systems, (ii) establishes a consensus sequence and polymorphic positions (PP) for each domain, and (iii) analyzes the complete coding sequence of an IC patient. With regard to the consensus, a high percentage of PP was observed in protease (PP=19%) and the X domain (PP=22%) within ORF1, the N-terminal region of the S domain (PP=22%) in ORF2, and the P1 (PP=35%) and P2 (PP=25%) domains in ORF3. In contrast, the ORF1 Y, ORF2 S, ORF2 M and ORF3 D1 domains were conserved in the reference sequences (0.40, 1, 0.70 and 0% of PP, respectively). The sequence from the IC patient had more mutations in the RpRp (D1235G, Q1242R, S1454T, V1480I, I1502 V, K1511R, G1373 V, E1442D, V1693 M), the terminal ORF2 S- domain (F10L, S26T, G36S, S70P, A105 V, I113 V), the X domain (T938 M, T856 V, S898A) and the helicase (S1014N, S975T, Q1133 K).
Subject(s)
Genome, Viral , Genomics/methods , Hepatitis E virus/genetics , Hepatitis E/virology , Humans , Mutation , Open Reading FramesSubject(s)
Aortic Diseases/prevention & control , Aspirin/administration & dosage , Endocarditis/prevention & control , Thrombosis/prevention & control , Animals , Aortic Diseases/microbiology , Aortic Diseases/pathology , Cardiac Catheterization , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endocarditis/microbiology , Endocarditis/pathology , Rabbits , Thrombosis/microbiology , Thrombosis/pathologyABSTRACT
Four oral penicillin V regimens were compared for the ability to prevent Streptococcus sanguis infection of experimentally induced valvular heart lesions in rabbits. Challenge doses of 10(4), 10(6), and 10(8) CFU of a penicillin-susceptible strain of S. sanguis were used in this study. Measured by recovery of test organisms from endocardial lesions, the lowest-concentration inoculum was infective for 53% of the recipients; the higher-concentration inocula were infective for all recipients. A single-oral-dose penicillin V regimen (36 mg/kg of body weight) prevented endocarditis when rabbits were challenged with 10(4) CFU, but protection diminished with increasing inoculum concentrations. In contrast, addition of a second penicillin V dose (18 mg/kg of body weight) administered with a 7-h interval between doses achieved fully effective prophylaxis against even the highest inoculum tested (10(8) CFU). A repeated set of experiments in which half the dose of penicillin V was administered showed significantly reduced protection against S. sanguis endocarditis.
