Viruses are a great threat to human life and health. Different viruses have its unique mechanism to efficiently infect cells, and the entry process and the nucleic acid replication using cell machine are two critical processes related to the fate of virus progeny. Real-time and long-term imaging techniques can be used to thoroughly investigate the viral infection events. This chapter will present the labeling of viral genomic RNA (gRNA) replication by developing new nanoprobes, one-donor-two-acceptors one, for example, in which the synergistic coupling of multiple energy transfer strategy, so as that the journey of viruses in live cells could be monitored and imaged in real time. Methods of labeling as well as that used for fluorescent and dark field scattering imaging are outlined.