In:
Journal of the International AIDS Society, Wiley, Vol. 22, No. 3 ( 2019-03)
Abstract:
The significant rise in incidence of Hepatitis C virus ( HCV ) infection among men‐who‐have‐sex‐with‐men ( MSM ) living with HIV ‐1 suggests that HCV under specific circumstances is transmitted via sexual contact. During sexual transmission HCV has to cross the epithelial barrier to either directly enter the blood stream or indirectly via mucosal immune cells. However, the mechanisms of sexual transmission of HCV remain unclear. We investigated the role of Langerhans cells ( LC s) in HCV susceptibility during sexual contact as LC s are among the first cells in mucosal tissues to encounter invading viruses. Methods We investigated the phenotype of primary LC s in anal biopsies from MSM living with HIV ‐1. To investigate the role of primary LC s in HCV infection and transmission, we have used both isolated primary skin LC s and the ex vivo tissue transmission model. Results Our data identified an important role for mucosal LC s in facilitating HCV transmission after HIV ‐1 exposure or immune activation. LC s were detected within mucosal anal tissues obtained from HIV ‐1 positive MSM biopsies. In order to perform functional studies, we used primary LC s from skin, which have a similar phenotype as mucosal LC s. Immature LC s were neither infected nor transmitted HCV to hepatocytes. Notably, exposure to HIV ‐1 significantly increased HCV transmission by LC s in the ex vivo transmission model. HIV ‐1 replication was crucial for the increased HCV transmission as HIV ‐1 inhibitors significantly reduced HIV ‐1‐induced HCV transmission. Moreover, tissue immune activation of LC s also increased HCV transmission to target cells. Conclusions Thus, our data strongly indicate that HIV ‐1 or immune activation in MSM leads to capture of HCV by mucosal LC s, which might facilitate transmission to other cells or allow entry of HCV into the blood. This novel transmission mechanism by LC s also implicates that the activation state of LC s is an important cellular determinant for HCV susceptibility after sexual contact.
Type of Medium:
Online Resource
ISSN:
1758-2652
,
1758-2652
DOI:
10.1002/jia2.2019.22.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2467110-1
