Herpesviridae Infections; Viruses
Viruses have evolved exquisite mechanisms for avoiding the host immune responses. Understanding these mechanisms can lead to a better understanding of both disease and how the immune system works. My lab exploits human and non-human oncogenic herpesviruses to help uncover new approaches to improve human health.
Extensive Research Description
Through co-evolution with their hosts, viruses have acquired exquisite mechanisms for coping with the anti-viral immune responses. Our lab is interested in detailing these viral coping mechanisms and examining their importance to pathogenicity, with the eventual goal of developing better prophylactic and treatment strategies. The major pathogens that we study are the gamma-herpesviruses, which include the most recently described human viral pathogen, Kaposi’s sarcoma-associated herpesvirus (KSHV). This virus is the causal agent of one of the most common AIDS-associated cancers in the Western world, as well as being a leading cause of cancer deaths in many regions of Africa. We are in the process of characterizing several gene products of KSHV that are able to modulate and block the host immune response. Among these proteins are K3 and K5, able to down regulate multiple key immunomodulatory proteins from the surface of expressing cells, including MHC class I, B7.2, ICAM-1 and CD31. Studies of the molecular mechanisms of action of these proteins have not only provided potential targets for anti-viral therapies, but have also provided insights into the mechanisms of cellular endocytosis, trafficking and host control of the immune response. Another facet of our research is the characterization of the host immune responses being made against the virus. To aid us in these studies, we are taking advantage of several animal models utilizing closely related ?-herpesviruses including murid ?-herpesvirus (MHV-68) of rodents, Herpesvirus saimiri (HVS) of New World non-human primates and rhesus rhadinovirus (RRV) of Old World non-human primates. In vitro gene expression and characterization experiments combined with in vivo infection experiments are allowing us to better describe the relationship between the virus and the host. These experiments have the promise of not only leading to a better understanding of the mechanisms of viral entry and tropism, but also to an understanding of what host responses are important to controlling viral infection, crucial in the design of anti-viral immunization strategies.Role of viral ubiquitin ligases in controlling the immune response.
Role of viral and cellular ubiquitin ligases in oncogenic progression and metabolism.
Role of viral and cellular ubiquitin ligases in control of apoptosis.
Mechanisms of viral entry, assembly and egress.
Role of herpesviruses in adverse pregnancy events.
Characterization of the Herpesvirus saimiri Orf51 protein
Means, R. E. Characterization of the Herpesvirus saimiri Orf51 protein. Virology. 2004 Aug 15326(1):67-78.
Complementing' viral infection: mechanisms for evading innate immunity
Lee, S. H., J. U. Jung, and R. E. Means*. 2003. 'Complementing' viral infection: mechanisms for evading innate immunity. Trends Microbiol 11:449-52.
Kaposi’s sarcoma associated herpesvirus immune evasion strategies
Means, R. E.*, S. M. Lang, Y. H. Chung, and J. U. Jung. Kaposi’s sarcoma associated herpesvirus immune evasion strategies. Frontiers in Biosciences. 2002. 7:e185-203
Multiple endocytic trafficking pathways of MHC class I molecules induced by a Herpesvirus protein
Means, R. E., S. Ishido, X. Alvarez, and J. U. Jung. Multiple endocytic trafficking pathways of MHC class I molecules induced by a Herpesvirus protein. EMBO J. 2002. 21:1-12.
Dendritic cell amplification of HIV type 1-specific CD8+ T cell responses in exposed, seronegative heterosexual women
Shacklett B. L., R. E. Means, M. Larsson, D. T. Wilkens, T. J. Beadle, M. J. Merritt, N. Bhardwaj, P. E. Palumbo, J. H. Skurnick, D. B. Louria, D. F. Nixon. Dendritic cell amplification of HIV type 1-specific CD8+ T cell responses in exposed, seronegative heterosexual women. AIDS Res Hum Retroviruses. 2002. 18(11):805-15.
Determinants of increased replicative capacity of serially passaged simian immunodeficiency virus with nef deleted in rhesus monkeys
Alexander, L., P. O. Illyinskii, S. M. Lang, R. E. Means, J. Lifson, K. Mansfield, and R. C. Desrosiers. 2003. Determinants of increased replicative capacity of serially passaged simian immunodeficiency virus with nef deleted in rhesus monkeys. J Virol 77:6823-35.
Resistance of Native, Oligomeric Envelope on Simian Immunodeficiency Virus to Digestion by Glycosidases
Means, R. E. and R. C. Desrosiers. Resistance of Native, Oligomeric Envelope on Simian Immunodeficiency Virus to Digestion by Glycosidases. J. Virol. 2000. 74(23):11181-90.
A role for carbohydrates in immune evasion in AIDS
Reitter, J. N., R. E. Means, and R. C. Desrosiers. A role for carbohydrates in immune evasion in AIDS. Nat Med. 1998. 4:679-84.