Annual Meeting of the Missouri Valley Branch of the American Society of Microbiology

Infectious diseases still remain the second leading cause of death worldwide, representing therefore a major public health challenge. My research focuses on evolutionary genetics and population dynamics of various pathogenic microorganisms: Human Immunodeficiency Virus-1 (HIV-1), Mycobacterium tuberculosis, Neisseria gonorrhoeae and Plasmodium parasites. Understanding these parameters is relevant to implement better prevention and control strategies. As examples of these challenges, I will discuss the ones we face in HIV-1 infection. Viral reservoirs in addition to HIV compartmentalization and rapid virus evolution represent a major obstacle in antiretroviral treatment. For this work, I will show that human follicular dendritic cells (FDCs) serve as a significant HIV reservoir and that virus diversity and compartmentalization in secondary lymphoid tissues may be greater than previously appreciated. I will also show that the outcome of HIV-1 evolution in a case of monozygotic twins was remarkably different, given the identical host genetic background and the identical source and timing of HIV-1 infection. Molecular Mechanisms for Poxvirus Host Range by Species-Specific Interactions with the Antiviral Protein Kinase PKR Stefan Rothenburg Kansas State University, Manhattan, KS 66506, USA; [email protected] Poxviruses are widespread pathogens, which display extremely different host ranges and virulence. Like many other animal viruses, poxviruses enter host cells via binding to receptors that are found in many different species. However, successful replication of poxviruses depends on the effective manipulation of the cell’s innate immune response. Some poxviral genes have been shown to confer host tropism in experimental settings and are thus called host range genes. K3L and E3L are two host range genes that have been well characterized in vaccinia virus. K3L was shown to be important for vaccinia virus infection of hamster but not human cells, whereas E3L was important for vaccinia virus replication in human but not in hamster cells. The molecular basis for this host range function was unknown. Both K3L and E3L proteins target the host antiviral protein kinase PKR. We demonstrate rapid evolution of PKR in vertebrates and that positive selection influenced the sensitivity of PKR to poxvirus inhibition. Moreover, PKR from different species varied greatly in their sensitivity to poxvirus inhibition, which provides a molecular explanation for the range gene function of poxvirus PKR inhibitors. The implication of our findings for the study of host-virus interactions will be discussed.