Polymorphisms matter!

PhD student Doug Fischer published part of his thesis project in the Journal of Virology ("CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes"). As we still do not understand how HIV-1 infects non-dividing cells, such as macrophages, Doug characterized a virus with a mutation in the capsid protein (N57A) that abolished the ability of HIV to infect non-dividing cells. In a collaboration with Masa Yamashita's lab, Doug showed that two widely used HIV-1 molecular clones (NL4-3 and LAI) that differ by 4 amino acids in the capsid protein had significantly different N57A infectivity phenotypes. Defects in N57A HIV-1 infection occurred at different steps of the early viral life cycle, depending on which strain was used. These 2 HIV-1 strains are representative of viruses in HIV-infected people. Our work suggests that significant differences can occur when using different HIV-1 strains, which are caused by natural polymorphisms. Congratulations, Doug!