In 2009, a panel of scientists headed by Kevin Weeks of the University of North Carolina managed to decode the full structure of the HIV-1 genome by means of a technique called SHAPE (selective 2′-hydroxyl acylation analyzed by primer extension). A report on the findings was published in the August 2009 issue of Nature, fleshing out the structure and function of the genome. Accordingly, the comprehensive study yielded the following conclusions:
1. The HIV-1 genome is encoded by a single-stranded RNA which does not come across as a linear framework, but it exhibits a convoluted structure. The RNA acts as an activator or a as a repressor to control the transmission of genetic information, expedite the formation of a single genomic dimmer, institutes reverse transcription, addresses virion packaging, addresses the split a sequence of nucleotides in DNA or RNA into three letter codons, pinpoints any changes in the RNA molecule and it reacts with viral and host proteins.
2. High-throughput SHAPE analysis has revealed that the HIV-1 genome comprises nine open reading frames that produce 15 proteins among which one can mention the matrix (MA), capsid (CA), nucleocapsid (NC), p6 proteins, protease (PR), reverse transcriptase (RT), integrase (IN), signal peptide (SP), gp120, gp41, auxiliary proteins, non-covalent dimmers or nucleocapsid. A deeper look into the evolution and performance of these proteins evinces traces of sustained activities at the molecular level triggering the phenomenon of protein linkage.
3. Besides nucleotides and proteins, the HIV-1 genome contains independent RNA folding domains which include both small stem-loops and 21 complex structures. These less apparent or smaller structures facilitate the identification and extraction of the main parts of the genome and facilitate the overall functioning of the other components. Unstructured motifs and insulator helices can also be pinpointed in the HIV-1 genome. Critical components of the viral host evasion strategy, these ‘free’ structures lie in close proximity of the well-defined RNA folding domains and interact with the latter on a regular basis. As a matter of fact, a considerably high number of stable helices and uncategorized segments that function as structural insulators, separate RNA sequences, encoding length polymorphisms, from other components of the genome.
This major breakthrough in understanding how the HIV-1 a genome works and how it manages to ‘outsmart’ the human host has brought about two-fold results: it has increased the possibility of finding a cure and put all the pieces of the HIV puzzle together.
