HIV sensing by the immune system
The innate immune system is responsible for recognising pathogens in a non-specific manner. From an evolutionary perspective, the innate immune system emerged first before the antigen-specific adaptive system. It depends on proteins and phagocytic cells that recognise conserved sequences on foreign pathogens to destroy them. Dendritic cells (DCs) are an integral part of the innate immune system and constitute attractive cells for therapy. To further study innate immunity, scientists on the EU-funded HIV INNATE IMMUNITY (Toward an HIV-1 vaccine: molecular mechanisms regulating the cryptic innate immune response to HIV-1) project utilised HIV as a model. Since HIV-1 cannot naturally infect DCs, researchers used Vpx proteins found in other lentiviruses to render DCs susceptible to HIV infection. DC infection activated innate responses, which required the interaction between the viral capsid protein and the cellular protein cyclophilin A. This led to the secretion of type I interferons, the activation of adaptive immunity and prevented the virus from infecting T cells. Researchers hypothesised that the cryptic innate response against HIV is a crucial determinant of the ability of the immune system to control HIV infection. They went on to dissect the process of virus sensing and identified that the viral cDNA was essential for detection by the innate sensor cGAS. Overall, the discovery that DCs could mount innate responses against HIV has important clinical implications. This mechanistic insight into HIV sensing could be explored therapeutically for designing new immunological strategies against HIV-1 infection.
Keywords
HIV, innate immune system, dendritic cells, cDNA, cGAS
