DNA Confinement drives uncoating of the HIV Virus

The confinement of double stranded (ds) viral DNA molecules has long attracted the interest of physicists. The bacteriophage viruses are the classical example of viruses where large pressures are produced by viral DNA confinement (in the range of tens of atmospheres)[1]. The protein shell the capsid has to be very strong so as to withstand these enormous pressures. In this article we propose that DNA confinement forces play a very important role in a very different class of viruses, namely the retroviruses, such as HIV. Figure 1 shows a schematic cross section of a mature HIV virus. Maturation of an HIV virus starts from an immature spherical shell of about 10 Gag “polyproteins” that envelops both the genome molecules as well certain enzymes. This Gag protein has cationic domains that are spliced of during maturation, known as “NCp7” fragments that aggregate with the anionic RNA genome molecules through electrostatic interactions. Other fragments of the Gag polyprotein (“CA” fragments) form the inner capsid while the remainder of the Gag protein become part of the outer shell of the mature virus (see Fig 1). Upon infection, this outer shell fuses with the membrane of the infected cell and the mature conical capsid containing the viral RNA gets released into the host cytoplasm.