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.
OBJECTIVE
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.
Bélec
Laurent
L
Unité INSERM U430 (Immunopathologie humaine), hôpital Broussais, and Université Pierre and Marie Curie (Paris VI), Paris, France. laurent.belec@egp.ap-hop-paris.fr
Legoff
Jérôme
J
Si-Mohamed
Ali
A
Bloch
Francis
F
Mbopi Keou
François Xavier
FX
Becquart
Pierre
P
Matta
Mathieu
M
Prazuck
Thierry
T
Petite
Jean Pierre
JP
Gutmann
Laurent
L
Payan
Christopher
C
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000378:metabolism*; D000917:Antibody Formation; D001826:Body Fluids / Q000378:metabolism* / Q000821:virology*; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology; D012463:Saliva / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D014621:Vagina / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology*; D017201:Virus Shedding
D000914:Antibodies, Viral; C087035:E1 protein, Hepatitis C virus; D006454:Hemoglobins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012709:Serum Albumin; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus