Among sexually-transmitted infections, herpes simplex virus type 2 (HSV-2) is the largest contributor to increased acquisition of human immunodeficiency virus type 1 (HIV-1) during co-infection. We discovered that calcitonin gene-related peptide (CGRP), a mucosal neuropeptide secreted by peripheral pain neurons termed nociceptors that innervate all genital tissues, strongly inhibits infection of Langerhans cells (LCs; resident antigen-presenting cells in stratified epithelia) with HIV-1 and HSV-2, revealing for the first time the unexpected anti-viral roles of CGRP. Recently, we developed the ‘mucosa-on-chip’ microfluidic model that combines CGRP-secreting nociceptor neurons with genital epithelial cells and LCs. In this model, infected LCs relay HSV-2 to nociceptor axons, resulting in axonal degeneration and reduction in CGRP content.
We are seeking a post-doctoral fellow to explore the anti-viral roles of CGRP during HSV-2/HIV-1 coinfection using the ‘mucosa-on-chip’ model, which mimics the complex in-vivo neuroimmune landscape of mucosal tissues.
The main objective of the selected candidate will be to prove that an unrecognized mechanism, by which HSV-2 increases HIV-1 acquisition during co-infection, involves HSV-2-mediated dysregulation of mucosal CGRP secretion, thereby counteracting the protective anti-HIV-1 actions of CGRP.
The project will be performed in the laboratory of ‘Mucosal entry, persistence and neuro-immune control of HIV-1 and other viruses’, under the scientific supervision of Dr Yonatan GANOR. Our team specialized in the mechanisms of HIV-1 entry and persistence in human mucosal tissues and aims at elaborating novel anti-viral strategies against HIV-1 and other sexually transmitted viruses.