HIV-1 latency and the eradication of long-term virus reservoirs
The HIV-1 pandemic represents one of the great plagues in human history and a major challenge for medicine, public health and biological research. Infection with HIV-1 causes AIDS, a syndrome that was first described in 1981. Continuous research has allowed the development of effective treatments that have transformed HIV-1 infection from a fatal illness into a chronic disease. Currently, 25 different active compounds belonging to six different drug families have been developed. However, regardless of the use of highly active antiretroviral therapy (HAART), a cure is not yet achievable, and HIV-1 persistence in reservoirs represents the major obstacle for its eradication.
All lentiviruses can infect macrophage lineage cells, in which they generate a persistent infection. HIV-1 is a lentivirus that has developed a broader tropism, leading to preferential infection of CD4+ T cells, which are severely destroyed during the illness. This target provides two potential environments for the virus, allowing latency in resting CD4+ T cells and massive viral replication in activated cells. The molecular mechanisms that lead to HIV-1 reactivation have been characterized in detail, but the study of virus latency remains limited. Recently, the identification of factors that restrict retroviral infections, the characterization of chromatin structure in the setting of viral integration, the discovery of new systems that regulate gene expression (such as small interfering RNAs (siRNAs)) and the development of new techniques for analysing HIV-1 latency have provided a new perspective on this concealed state. Latency should not be considered a merely passive event but, rather, an active process that is maintained by cellular elements. This review analyses the molecular mechanisms that are necessary for the establishment of HIV-1 latency and their relationships with different cellular and anatomical reservoirs, and discusses the current treatment strategies for targeting viral persistence in reservoirs, their main limitations and future perspectives.
Related:
- Why is HIV a pathogen?
- How does HIV cause AIDS?
- Immune exhaustion in HIV infection
- HIV “can never be cured”
- HIV-2 – a kinder AIDS virus?
Tags: Biology, disease, Health, HIV/AIDS, Immunology, Medicine, Microbiology, Science, Virology, virus
