TY - JOUR
T1 - HIV-1 exposure and immune activation enhance sexual transmission of Hepatitis C virus by primary Langerhans cells
AU - Nijmeijer, Bernadien M.
AU - Sarrami-Forooshani, Ramin
AU - Steba, Gaby S.
AU - Schreurs, Renee R. C. E.
AU - Koekkoek, Sylvie M.
AU - Molenkamp, Richard
AU - Schinkel, Janke
AU - Reiss, Peter
AU - van Heukelom, Matthijs L. Siegenbeek
AU - van der Valk, Marc
AU - Ribeiro, Carla M. S.
AU - Geijtenbeek, Teunis B. H.
N1 - © 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Introduction: 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 (LCs) in HCV susceptibility during sexual contact as LCs are among the first cells in mucosal tissues to encounter invading viruses. Methods: We investigated the phenotype of primary LCs in anal biopsies from MSM living with HIV-1. To investigate the role of primary LCs in HCV infection and transmission, we have used both isolated primary skin LCs and the ex vivo tissue transmission model. Results: Our data identified an important role for mucosal LCs in facilitating HCV transmission after HIV-1 exposure or immune activation. LCs were detected within mucosal anal tissues obtained from HIV-1 positive MSM biopsies. In order to perform functional studies, we used primary LCs from skin, which have a similar phenotype as mucosal LCs. Immature LCs were neither infected nor transmitted HCV to hepatocytes. Notably, exposure to HIV-1 significantly increased HCV transmission by LCs 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 LCs 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 LCs, which might facilitate transmission to other cells or allow entry of HCV into the blood. This novel transmission mechanism by LCs also implicates that the activation state of LCs is an important cellular determinant for HCV susceptibility after sexual contact.
AB - Introduction: 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 (LCs) in HCV susceptibility during sexual contact as LCs are among the first cells in mucosal tissues to encounter invading viruses. Methods: We investigated the phenotype of primary LCs in anal biopsies from MSM living with HIV-1. To investigate the role of primary LCs in HCV infection and transmission, we have used both isolated primary skin LCs and the ex vivo tissue transmission model. Results: Our data identified an important role for mucosal LCs in facilitating HCV transmission after HIV-1 exposure or immune activation. LCs were detected within mucosal anal tissues obtained from HIV-1 positive MSM biopsies. In order to perform functional studies, we used primary LCs from skin, which have a similar phenotype as mucosal LCs. Immature LCs were neither infected nor transmitted HCV to hepatocytes. Notably, exposure to HIV-1 significantly increased HCV transmission by LCs 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 LCs 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 LCs, which might facilitate transmission to other cells or allow entry of HCV into the blood. This novel transmission mechanism by LCs also implicates that the activation state of LCs is an important cellular determinant for HCV susceptibility after sexual contact.
KW - HIV-1
KW - Langerhans Cells
KW - Hepatitis C virus
KW - Immune activation
KW - Viral transmission
KW - Men-who-have-Sex-with-Men
KW - Mucous Membrane/immunology
KW - Hepacivirus/genetics
KW - Hepatitis C/epidemiology
KW - Humans
KW - Cells, Cultured
KW - Male
KW - Sexually Transmitted Diseases/immunology
KW - HIV Infections/complications
KW - HIV-1/genetics
KW - Adult
KW - Langerhans Cells/immunology
UR - http://www.scopus.com/inward/record.url?scp=85063678786&partnerID=8YFLogxK
U2 - 10.1002/jia2.25268
DO - 10.1002/jia2.25268
M3 - Article
C2 - 30932366
SN - 1758-2652
VL - 22
JO - Journal of the International AIDS Society [E]
JF - Journal of the International AIDS Society [E]
IS - 3
M1 - e25268
ER -