Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

HIV: still a global problem requiring prevention and cure (#5)

Anthony Cunningham 1 2 , Andrew Harman 1 2 , Najla Nasr 1 2 , Orion Tong 1 2 , Kirstie Bertram 1 2 , Kerrie Sandgren 1 2 , Heeva Baharlou 1 2
  1. The Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. University of Sydney, Sydney, Australia

Despite the rollout of antiretroviral therapy (ART) around the world HIV continues to produce a major global health burden. Although ART has resulted in a 50% reduction in AIDS related deaths since the peak in 2004, in 2017-18, WHO estimated there were 1.8 million new infections globally and that only 21 million of 37 million people currently infected are on ART. ART can also be given to healthy individuals at high risk of acquiring HIV as pre-exposure prophylaxis (PrEP) which has been successfully deployed in Australia but not in high HIV incidence countries. Prior infection with Herpes simplex virus type 2 enhances HIV acquisition three fold. Therefore, a vaccine against HIV (and possibly HSV2) is required to prevent HIV transmission and a cure is needed so people can safely stop ART. For vaccine development, we need a better understanding of how HIV (and HSV) initially penetrate both inflamed and uninflamed anogenital mucosa and interact with resident (innate) immune cells.

We recently demonstrated that HIV and HSV first encounter and replicate in Langerhans cells and a new type of (CD11c+) dendritic cell (DC) in human genital mucosa (Nature Comms 2019). These DCs can transfer HIV to CD4 T cells which infiltrate the dermis leading to rapid systemic spread or initiation of a latently infected T cell reservoir which persists for life. Type I IFNs are induced early in HIV/SIV infection in humans, and macaques and can limit HIV spread and the size of the reservoir. However HIV inhibits IFN-I production in the initial target dendritic cells (DCs), but this may be restored after subsequent infiltration of plasmacytoid DCs. HIV then develops resistance to IFNs. Preventing the initial IFN inhibition by HIV is a strategy to reduce the likelihood of HIV obtaining a ‘toehold’ in its target cells. HSV differs in being transferred to dermal DCs before stimulating CD4 and CD8 cells. Further definition of this pathway will assist HSV vaccine development