TY - JOUR
T1 - HIV-1 subverts the complement system in semen to enhance viral transmission
AU - Nijmeijer, Bernadien M.
AU - Bermejo-Jambrina, Marta
AU - Kaptein, Tanja M.
AU - Ribeiro, Carla M. S.
AU - Wilflingseder, Doris
AU - Geijtenbeek, Teunis B. H.
N1 - Funding Information: We are grateful to the Boerhaave Medical Centre (Amsterdam, the Netherlands) and A. Knottenbelt (Flevo Clinic Almere, the Netherlands) for the provision of human skin tissues. This work was supported by Aidsfonds [P-11118], European Research Council, Advanced grant [670424], and Dutch Scientific organization NOW [VIDI 91718331]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021, The Author(s).
PY - 2021/5
Y1 - 2021/5
N2 - Semen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission.
AB - Semen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission.
UR - http://www.scopus.com/inward/record.url?scp=85100961898&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41385-021-00376-9
DO - https://doi.org/10.1038/s41385-021-00376-9
M3 - Article
C2 - 33568786
SN - 1933-0219
VL - 14
SP - 743
EP - 750
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 3
ER -