Scientists successfully unraveled the lifecycle of HIV  

Despite being recently covered by the global epidemic of COVID-19, humanity is still facing an epidemic of another disease, AIDS, with approximately 38 million people living with HIV worldwide, according to UNAIDS. Many people have died as a result of HIV infection since the epidemic began in the 1980s.

Researchers from Germany have recently developed a new technique that may be able to analyze and influence key stages of the HIV lifecycle, with the results of the study "Short- and long-range interactions in the HIV-1 5' UTR regulate genome dimerization and packaging" published in Nature Structural & Molecular Biology.

Critical stages of the viral life cycle are appealing targets for drugs and therapies, making basic research to understand and affect the underlying molecular mechanisms all the more important. A distinctive feature of HIV-1 mutants is that they contain two copies of the viral genome, which can be brought together during viral replication by a process called dimerization which is also a prerequisite for viral packaging and can ultimately lead to the production of novel infectious viral particles and the conduct of the complete viral replication process.

In this study, the researchers describe a novel technique that can investigate the HIV-1 life cycle at single nucleotide resolution, a method called FARS-seq (Functional Analysis of RNA Structure) that may help researchers identify regions of the HIV-1 genome that are important for dimerization and viral packaging. Researcher Professor Redmond Smyth explained that dimerization is a prerequisite for viral packaging, which has been discussed for a long time in HIV-1 research, however, the molecular mechanisms behind it are currently unknown to researchers, and the study in this paper provides this information at high resolution, which may also hold promise for targeted interventions.

The results of this study show that the HIV-1 genome exists in two different RNA conformations, only one of which is involved in the genome packaging process, and the second conformation, in which the RNA stays in the host cell and is subsequently translated into new viral proteins, thus acting as a molecular switch that guides the fate of viral RNA and the replication process of the virus. Now that scientists have identified sequences that regulate the balance between the two RNA conformations, this study reveals how virulence factors bind to these regions and can be used to target or interfere with viral assembly.

The researchers say they hope to use these findings to develop RNA-based antiretroviral drugs or improved gene therapy vectors, and in the next study, the researchers would like to determine if these observations apply to other HIV strains as well through more in-depth studies. The findings of this paper, taken together, may provide fresh insights into the HIV-1 life cycle as well as a molecular explanation for the link between RNA dimerization and packaging.