The human immunodeficiency virus (HIV) is a lentivirus which, by infecting CD4 T lymphocytes, is responsible for acquired immunodeficiency syndrome (AIDS), characterized by opportunistic infections, encephalopathy and tumors leading, in the absence of treatment, to death within a few years. The biology of the virus, isolated in 1983 and cloned in 1985, is now well understood. Its mode of entry (CD4 membrane receptors and CCR5 or CXCR4 chemokine receptors), the integration of its genetic material into the genome of the infected cell after retrotranscription of viral genomic RNA, the conditions under which these components are produced, virion assembly and production have all been well characterized. The epidemiology of the infection is also well known. To date, 37 million people are infected worldwide, 95% of whom live in poor countries, 50% of whom are women and 9% children. Two million new cases occur every year. To date, just over half of patients are treated with combination antiretroviral chemotherapy, a long way from the WHO's "90/90/90" target: 90% of patients diagnosed, 90% treated and 90% in clinical remission. The ways in which the virus is transmitted via mucous membranes or blood, and the associated risk factors, have also been well determined. During infection, there is a rapid loss of CD4 T lymphocytes, either directly as a result of the lytic effect of viral replication, or indirectly through chronic lymphocyte activation. It is estimated that around1010 viral particles are produced (and destroyed by the immune system) every day, explaining the infection's capacity to spread to mucosal lymphoid tissues and secondary lymphoid organs rich in CD4 T cells. The organism seeks to limit the infection by bringing into play multiple immune effectors: factors that restrict the viral cycle through innate immunity, against which the virus has developed "countermeasures"; adaptive B and T responses, particularly cytotoxic ones, which we now know depend on early and intense activation after the onset of infection, as discussed below. This response is essentially inadequate, however, due to several critical factors: a) infection and destruction of cells involved in immune responses, b) high mutation rate of the virus due to the "infidel" nature of reverse transcriptase, which enables it to evade immune responses by selecting mutants. These characteristics also explain the failure to date of attempts to protect the virus by vaccination.
15:00 - 16:30
Lecture
HIV infection, a defeat of the immune system ? (I)
Alain Fischer
15:00 - 16:30
