Seema S. Lakdawala, PhD
439 Bridgeside Point II
450 Technology Drive
PhD in Biological Sciences, University of California San Diego
Influenza A viruses pose a major public health risk from seasonal epidemics and sporadic pandemics. Our lab studies the molecular properties contributing to the epidemiological success of influenza A viruses to better predict future pandemics. There are two main areas of research in my lab 1) exploring the intracellular dynamics of influenza viral RNA assembly and 2) defining the viral properties necessary for efficient airborne transmission of influenza viruses.
Influenza A viruses contain eight single stranded RNA segments. Reassortment of the influenza viral genome in co-infected cells confers an evolutionary advantage for the virus, and can result in viruses with pandemic potential like the 2009 pandemic H1N1 and 2013 H7N9 virus. Replication of the viral genome occurs in the nucleus of the host cell and the progeny viral RNA (vRNA) segments must be transported to the plasma membrane for budding. The dynamics of vRNA assembly into progeny virions remains unknown. We used sophisticated microscopy techniques to visualize the 3D-localization of four distinct vRNA segments in an infected cell and a fluorescent virus to visualize vRNA transport during a productive infection to determine where, when and how assembly occurs. Our data suggest that vRNA segments are exported from the nucleus as subcomplexes that undergo additional assembly en-route to the plasma membrane through dynamic fusion events of vRNA-containing cytoplasmic foci. These observations have broad implications for understanding the intracellular requirements behind reassortment of influenza viruses and may lead to the development of new antiviral targets.
Airborne transmission of influenza viruses is critical for rapid spread of the virus during epidemics and pandemics. We have established a method to study the transmissibility of influenza viruses via the airborne route using ferrets, which are naturally susceptible to human influenza viruses. Using a loss-of-function approach we will define the viral properties necessary for transmission of seasonal H1N1 and H3N2 viruses. In addition, we will test the role of different therapeutic platforms on limiting the spread of influenza via aerosols.
Combining these two areas of research we will be able to develop a comprehensive surveillance system to determine the pandemic potential of circulating zoonotic influenza viruses, which will be useful in all areas of pandemic preparedness.
Research Lab Affiliation
Areas of Interest
Lakdawala S.S, Jayaraman A, Halpin R.A, Lamirande E.W, Shih A.R, Stockwell T.B, Lin X, Simenauer A, Hanson C.T, Vogel L, Paskel M, Minai M, Moore I, Orandle M, Das S.R, Wentworth D.E, Sasisekharan R. and Subbarao K. (2015) The soft palate is an important site of adaptation for transmissible influenza viruses. Nature. 526: 122-125. | View Abstract
Lakdawala S.S, Wu Y, Wawrzusin P, Kabat J, Broadbent A.J, Lamirande E.W, Fodor E, Altan-Bonnet N, Shroff H. and Subbarao K. (2014) Influenza a virus assembly intermediates fuse in the cytoplasm. PLoS Pathog. 10: e1003971. | View Abstract
Lakdawala S.S, Shih A.R, Jayaraman A, Lamirande E.W, Moore I, Paskel M, Sasisekharan R. and Subbaro K. (2013) Receptor specificity does not affect replication or virulence of the 2009 pandemic H1N1 influenza virus in mice and ferrets. Virology. 446: 349-356. | View Abstract
Lakdawala S.S. and Subbarao K. (2012) The ongoing battle against influenza: The challenge of flu transmission. Nat Med. 18: 1468-1470. | View Abstract
Lakdawala S.S, Lamirande E.W, Suguitan A.L., Jr., Wang W, Santos C.P, Vogel L, Matsuoka Y, Lindsley W.G, Jin H and Subbarao K. (2011) Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus. PLoS Pathog 7: e1002443. | View Abstract
Luke C, Lakdawala S.S. and Subbarao K. “Chapter 16: Influenza Vaccine-Live” VACCINES, Sixth Edition, Elsevier. |