Retroviral Recombination and Virus Assembly

Retroviral Recombination and Virus Assembly
This research is focused on understanding the mechanisms of retroviral recombination and virus assembly.

Recombination plays an important in HIV replication and evolution. For example, many of the primary isolates of HIV are recombinants, and recombination can assort mutations to generate variants that escape host immune response or are resistant to multidrug treatment protocols.

Unique among virus families, retroviruses package two copies of viral RNA in their virus particles, with each copy containing the complete genome. Upon infection, viral-encoded reverse transcriptase can use portions of each copackaged RNA genome as templates to generate a DNA copy that is recombinant. Because of this mechanism, novel recombinants can only be generated from virions that have two copies of genetically different RNAs (heterozygous virions). Heterozygous virions are strictly produced from cells that are infected by more than one related retrovirus (double infection). To gain a better understanding of the recombination process, we are studying: 1) the dynamics of HIV infection and double infection, and 2) the mechanisms and frequencies of HIV recombination.

Dynamics of HIV infection and double infection. We have demonstrated that HIV-1 infection and double infection are nonrandom. Double infection of HIV-1 occurs at frequencies much higher than expected from random events. We have hypothesized that the varied infectivity in the target cell populations causes nonrandom double infection. We will delineate the mechanisms of nonrandom infection and double infection, and examine factors that affect infection. Results from these studies would shed light on not only the double infection process but also the general dynamics of HIV infection