Figure 1a: Cellular life cycle of rabies virus.

In the first phase of the rabies virus (RABV) life cycle, the virus binds to the cell surface receptors via its glycoprotein and enters by endocytosis (step 1). Subsequently, the viral membrane fuses with the endosomal membrane to release the viral genome (uncoating, step 2). In the second phase, the encapsidated negative-stranded RNA genome is transcribed by the polymerase complex, starting with a short uncapped leader RNA (leRNA), followed by the transcription of 5′ end-capped (cap) and polyadenylated (A) mRNAs, and their translation into the viral proteins nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and polymerase (L) (steps 3 and 4). Following replication, the full-length antigenomic RNA is encapsidated in the nucleoprotein protein along with the genomic RNA. The synthesized antigenome functions as a template for the synthesis of additional copies of genomic RNA (step 5). In the last phase, the viral components are assembled and the RABV virions bud and are released, starting a new round of infection (step 6).