Dr. Thali received his Ph.D. degree from the University of Zürich, Switzerland in 1990 under the direction of Dr.W. Schaffner. He did postdoctoral research at Harvard Medical School/Dana-Farber Cancer Institute with Dr. J. Sodroski and was an Assistant Professor at the University of Lausanne. He is currently an Associate Professor at the Department of Microbiology and Molecular Genetics, and he served as chair of the College of Medicine Graduate Education Committee and the director of the CMB Program from 2006 to 2009.

Research Interests

Molecular regulation of HIV-1 assembly, release an cell-to-cell transmission
Successful dissemination of HIV-1 in infected individuals depends on efficient transmission of viral particles from infected (producer) to uninfected (target) cells. In vitro propagation studies have established that HIV-1 particles are most effectively transmitted to target cells if they bud at the so-called virological synapse (VS) that forms between producer and target cells. Such synaptic virus transmission is thought to be prevalent also in vivo, when HIV-1 spreads in secondary lymphoid organs of infected individuals. The events leading to the formation, maintenance and disassembly of the VS are poorly understood.

Our laboratory is investigating mechanisms that control the synaptic transmission of HIV- 1. Together with other groups we have shown that this virus exits from infected cells at membrane segments that are enriched in tetraspanins and we are thus trying to define what roles these cellular scaffold proteins play during HIV-1 transmission from cell-to-cell. So far we found that tetraspanins, though present at viral budding sites, are not needed for particle release. Indeed, these proteins, when acquired by newly formed viral particles, even reduce the infectivity of virions (see also Sato et al., 2008, J Virol 82:1021). However, while their presence at HIV-1 exit sites thus appears detrimental to viral spread, we also found that these proteins prevent the formation of syncytia that can form when producer and target cells fuse. The virus may benefit from such fusion prevention, as it guaranties prolonged survival of newly infected cells. For this reason, but also because tetraspanins overall are downregulated in infected cells, we are currently testing the hypothesis that HIV-1 evolved to temporarily and spatially adjust the levels of tetraspanins such that they allow for sustained virus propagation.

Recently, we have also started to compare (at the molecular level) the assembly and release process of HIV-1 with that of influenza virus and we are further examining the characteristics of the two exit sites. In these investigations, as in the HIV-1 transmission analyses, we use a combination of virological and cell biological methods. Overall, we expect that our studies will provide further insight into the molecular mechanisms underlying the spread of pathogenic viruses.

Finally, while our research endeavor primarily aims at characterizing steps in the replication cycle of HIV and influenza virus that may serve as targets for the development of anti-viral strategies, we try not to lose sight of the big picture. The classical definition of viruses as “obligate intracellular parasites” clearly does not render justice to these genetic entities. Irrespective of whether or not the host immune system can control their levels of replication, relatively few viruses cause disease, and it is now clear that viruses and virus-like elements played important roles at the early stages of life and throughout evolution. Understanding what viruses really are will not only be interesting per se, it will also lead to a better understanding of how some of them can inflict harm.

Selected Publications

Nydegger, S, Khurana, S, Krementsov, DK, Foti, M, Thali, M. Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1. J Cell Biol. 2006 Jun 5;173(5):795-807.

Khurana, S., Krementsov, DN, de Parseval, A, Elder JH, Foti, M, Thali, M Human immunodeficiency virus type 1 and influenza virus exit via different membrane microdomains. J Virol. 2007 Nov;81(22):12630-40. Epub 2007 Sep 12.

Singethan K, Müller N, Schubert S, Lüttge D, Krementsov DN, Khurana SR, Krohne G, Schneider-Schaulies S, Thali M, Schneider-Schaulies J. CD9 clustering and formation of microvilli zippers between contacting cells regulates virus-induced cell fusion. Traffic. 2008 Jun;9(6):924-35. Epub 2008 Mar 17.

Thali M. The roles of tetraspanins in HIV-1 replication (review). Current Topics in Microbiology and Immunology. in press.

Weng J, Krementsov DN, Khurana S, Roy NH, Thali M. Formation of syncytia is repressed by tetraspanins in human immunodeficiency virus type 1-producing cells. J Virol. 83 (2009):7467-74.

CMB Lab Members