Abstract
Genital mucosal transmission is the most common route of HIV spread. The initial responses triggered at the site of viral entry are reportedly affected by host factors, especially complement components present at the site, and this will have profound consequences on the outcome and pathogenesis of HIV infection. We studied the initial events associated with host-pathogen interactions by exposing cervical biopsies to free or complement-opsonized HIV. Opsonization resulted in higher rates of HIV acquisition/infection in mucosal tissues and emigrating dendritic cells. Transcriptomic and proteomic data showed a significantly more pathways and higher expression of genes and proteins associated with viral replication and pathways involved in different aspects of viral infection including interferon signaling, cytokine profile and dendritic cell maturation for the opsonized HIV. Moreover, the proteomics data indicate a general suppression by the HIV exposure. This clearly suggests that HIV opsonization alters the initial signaling pathways in the cervical mucosa in a manner that promotes viral establishment and infection. Our findings provide a foundation for further studies of the role these early HIV induced events play in HIV pathogenesis.
Highlights
The most common mode of HIV-1 spread is through heterosexual intercourse, and a vast majority of new infections globally occur in females
We found that the infection levels of the cervical mucosal tissue and emigrating immune cells were enhanced after exposure to complementopsonized HIV and complement and antibody-opsonized HIV compared to free HIV
The cervical biopsies were exposed to mock, F-HIV, complement-opsonized HIV (C-HIV) and complement and antibody opsonized HIV (CI-HIV) and cultured between 6h to 5 days
Summary
The most common mode of HIV-1 spread is through heterosexual intercourse, and a vast majority of new infections globally occur in females. Immunobiological investigations of HIV infection involving the cervical mucosa are of paramount importance, especially to better understand the events associated with initial infection as well as viral dissemination in the host. To attain successful establishment of infection in the host, HIV virions need to cross the genital mucosal barrier and/or encounter certain immune cells that can transfer the viruses to target cells in the epithelium [1, 2]. Evidence suggests that 24h following exposure, dendritic cells (DCs) with captured virions reach the draining lymph nodes where they transfer infectious HIV to bystander cells [2, 3]. The primary target cells of HIV and productive viral infection appear to be tissue-resident memory (TRM) CD4+ T cells [3]
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