Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun 130062, China. Electronic address: [Email]
Rabies virus (RABV), an enveloped virus with a single-stranded and negative-sense RNA genome, is the type species of the Lyssavirus Genus within the Rhabdoviridae family. As the causative agent of rabies with a nearly 100% fatality, the neurotropic RABV pose a serious threat to the global public health. Though a great effort has been made toward understanding the molecular mechanism underlying virus infection cycle, there are still many aspects need to be elucidated, especially on the early events during virus replication cycle. With the application of the multiple advanced technologies, much progress has been made on these aspects. To date, multiple receptors, such as nAChR, NCAM, p75NTR, mGluR2, carbohydrates, and gangliosides, have been identified. Following initial attachment, RABV internalization occurs through clathrin-mediated endocytosis (CME) with the help of actin. After viral entry, intracellular trafficking occurs. Two retrograde trafficking models, stating that either whole virions are parceled into vesicles or only the viral capsids are transported, have been proposed. Moreover, complete enveloped virions or G-containing vesicle-associated ribonucleoproteins (RNPs) may be formed during anterograde transport, which remains poorly characterized but is important for viral budding. Combining the data elucidating the molecular mechanisms of RABV attachment, entry, and intracellular trafficking, this review provides an integrated view of the early events in the viral life cycle.