Cell-associated, non-replicating strand(+) hepatitis C virus-RNA shedding in cervicovaginal secretions from chronically HCV-infected women.

BACKGROUND: Lack of mucosal hepatitis C virus (HCV) transmission may be due to fairly low infectivity of body fluids in HCV-infected individuals in association with yet unknown innate or acquired resistance factors in individuals exposed to the virus. OBJECTIVE: To evaluate HCV excretion patterns in cervicovaginal secretions obtained from chronically HCV-infected women. STUDY DESIGN: Fifteen chronically HCV-infected women of childbearing age hospitalized for chronic hepatitis were prospectively recruited. Cervicovaginal secretions were obtained by vaginal washing with 3 ml phosphate-buffered saline (PBS). All cervicovaginal secretions were free of hemoglobin traces and also free of semen traces. Free HCV-RNA and cell-associated HCV-RNA were examined in acellular part and cellular part of the cervicovaginal secretions, respectively, by in-house qualitative PCR for 5'-HCV-non-coding region (NCR). Negative strand HCV-RNA, a marker of HCV replication, was searched by using tag-RT-nested PCR (tag-RT-NPCR). RESULTS: HCV-RNA could not be detected in the acellular fractions of the 15 evaluated cervicovaginal secretions. In contrast, HCV-RNA could be detected in the cellular fractions of four of 15 (27%) cervicovaginal secretions. None of the cervicovaginal secretions, including the four positive cell-associated HCV-RNA, contained negative strand, replicating HCV-RNA. CONCLUSIONS: Our results suggest that positive strand HCV-RNA may be present outside the menstruation periods as cell-associated virus in the cervicovaginal secretions of a minority of untreated HCV-seropositive, HCV-RNA-viremic women, and that the lower female genital tract does not constitute a reservoir where HCV replicates. These observations thus provide the basis for the low risk of female-to-male sexual transmission of HCV infection.

Mucosal humoral immune response to hepatitis C virus E1/E2 surface glycoproteins and HCV shedding in saliva and cervicovaginal fluids from chronically HCV-infected patients.

BACKGROUND/AIMS: We herein focused on identifying biological factors possibly involved in non-parenteral transmission of hepatitis C virus (HCV), such as HCV excretion patterns and antibody-based immunity to the virus in saliva and/or cervicovaginal secretions (CVS). METHODS: Paired blood, saliva and cervicovaginal lavage samples were obtained from HCV-RNA plasma-positive hemoglobin (Hb) antigen and HIV-seronegative, HCV-seropositive males (n=13) and females (n=21). HCV-specific antibodies were detected by ELISA in paired samples, and HCV-RNA was detected in cell-free and cell-associated body fluids. RESULTS: Antibodies to E1 HCV surface glycoprotein of the IgG and IgA isotypes showed similar, but less pronounced, profiles as IgG and IgA to E2. HCV-specific IgG and IgA in mucosal fluids likely originated predominantly from the systemic compartment, because HCV-specific mucosal immunoglobulins involved primarily monomeric antibodies, including monomeric IgA, and because their specific activities for HCV antigens in corporeal fluids were similar to those in paired serum (Se). Viral shedding in saliva or CVS was restricted to cell-associated, non-replicating strand((+)) HCV-RNA in 42% (12 out of 28) of saliva and in 19% (four out of 21) of cervicovaginal fluids. CONCLUSIONS: The association in body fluids of HCV-specific IgG, and to a lesser extent IgA, directed to E1/E2 surface glycoproteins (which may block critical steps of virus-cell interactions), of undetectable free viral RNA, and of occasional non-replicating cell-associated HCV, suggests a resulting poor infectivity of saliva or cervicovaginal fluid in chronically HCV-infected individuals. Taken together, these observations provide the basis for the low risk of non-parenteral transmission of HCV infection.