Blocking of integrins significantly inhibits HIV-1 infection of human cervical mucosa immune cells and development of founder populations
2011 (English)Manuscript (preprint) (Other academic)
Slightly more than half of the HIV-1 infected individuals in the world are women and almost all acquire the infection through sexual intercourse. The initial interaction between HIV-1 and the host occurs at the mucosa site and the most common mode to access the submucosa is through dendritic cells (DCs). In the cervical mucosa, HIV-1 exist both as free and opsonized virions and this might influence initial infection. We used a cervical tissue explant model and both free and opsonized virions to study HIV-1 transmission and how it can be prevented.
We found that complement opsonization significantly enhanced HIV-1 infection of DCs compared to free HIV-1, but this increased infection was not seen for CD4+ T cells. Blocking of α4, β7, and β1 integrins demonstrated significant inhibition of infection of both DCs and CD4+ T cells emigrating from mucosa, independent of the use of free or complement opsonized HIV-1. We found a higher impairment of HIV-1 infection in emigrating DCs for complement opsonized virions compared to free virions when the use of αM/β2 and α4 integrins was blocked.
This study showed that block of integrins decreased the HIV-1 infection of both DCs and CD4+ T cells emigrating from the cervical explant tissues and, remarkably, the establishment of founder populations in these tissues. This indicates that preventing or severely lowering initial infection of the cervical mucosa could avert systemic HIV-1 infection and should be considered for development of microbicides to prevent HIV infection and transmission.
Place, publisher, year, edition, pages
Dendritic cells, complement opsonized HIV-1, antigen presentation
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-72342OAI: oai:DiVA.org:liu-72342DiVA: diva2:459221