Influenza virus exploits tunneling nanotubes for cell-to-cell spread
Author(s)Kumar, Amrita; Kim, Jin Hyang; Ranjan, Priya; Metcalfe, Maureen G.; Cao, Weiping; Mishina, Margarita; Gangappa, Shivaprakash; Guo, Zhu; Zaki, Sherif; York, Ian; García-Sastre, Adolfo; Sambhara, Suryaprakash; Boyden, Edward; Shaw, Michael; ... Show more Show less
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Tunneling nanotubes (TNTs) represent a novel route of intercellular communication. While previous work has shown that TNTs facilitate the exchange of viral or prion proteins from infected to naïve cells, it is not clear whether the viral genome is also transferred via this mechanism and further, whether transfer via this route can result in productive replication of the infectious agents in the recipient cell. Here we present evidence that lung epithelial cells are connected by TNTs, and in spite of the presence of neutralizing antibodies and an antiviral agent, Oseltamivir, influenza virus can exploit these networks to transfer viral proteins and genome from the infected to naïve cell, resulting in productive viral replication in the naïve cells. These observations indicate that influenza viruses can spread using these intercellular networks that connect epithelial cells, evading immune and antiviral defenses and provide an explanation for the incidence of influenza infections even in influenza-immune individuals and vaccine failures.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Massachusetts Institute of Technology. Department of Mathematics; Massachusetts Institute of Technology. Department of Physics; Massachusetts Institute of Technology. Media Laboratory; Program in Media Arts and Sciences (Massachusetts Institute of Technology)
Nature Publishing Group
Kumar, Amrita, Jin Hyang Kim, Priya Ranjan, Maureen G. Metcalfe, Weiping Cao, Margarita Mishina, Shivaprakash Gangappa, et al. “Influenza Virus Exploits Tunneling Nanotubes for Cell-to-Cell Spread.” Scientific Reports 7 (January 6, 2017): 40360.
Final published version