Two variants of Enterovirus-A71, a major causative agent of the hand foot and mouth disease, have been isolated in 2012 by our lab. One of them had the ability to infect the cerebrospinal fluid of a clinical patient due to mutation on the capsid protein, VP1-97R. The second variant had an additional mutation at position 167G of the same protein, acquired in vitro during passages on cells. Since then, several studies have been carried out to investigate the consequences of those mutations on the virus tropism. In the present study, the focus is placed on the cell-to-cell transmission, and their use of Tunneling nanotube, to investigate a potential difference between them. For this, we used a large variety of techniques, from fluorescent microscopy to molecular biology. This study, in line with the previous ones, is based on mouse adapted viruses, MP4, MP4-97R and MP4-97R/167G. We observed by immunofluorescence a clear presence of actin filaments and capsid of the three viruses in tunneling nanotubes. We co-cultured susceptible and non-susceptible cells and observed infection in non-susceptible cells, suggesting a viral transmission by contact. We did not observe any SCARB2 transmission to non-susceptible cells, suggesting a SCARB2-dependant viral infection. In parallel, the production of an mCherry expressing MP4-97R has been done to complete the collection of MP4 and MP4-97R/167G expressing mCherry virus available in the lab, for a live-cell imaging purpose. In conclusion, we established the beginning of a new research direction in the investigation of EV-A71 transmission and in the characterization of its variants, which will be continued by further experiments.