Rotavirus+Life+Cycle+Example

**Rotavirus Life Cycle** copied from [|Standford University]


 * Adsorption:**Rotaviruses attach to target cells using VP4 or its cleavage product, VP5*, but the initial binding is very nonspecific, involving cellular sialic acid (Knipe and Howley 1929). The specificity of rotaviruses for differentiated enterocytes of the small intestine probably comes from the interaction of VP8*, another cleavage product of VP4, with 2-//O//-methyl α-SA (Knipe and Howley 1930).

Rhesus rotavirus VP4[|(3)]

Rhesus Rotavirus VP4 complexed with 2-//O//-methyl alpha sialic acid[|(4)] **Penetration and Uncoating:**Rotavirus entry into the cell involves a series of conformational changes in the capsid proteins after binding with cellular receptors such as integrins. The detailed mechanism of penetration, however, remains unclear. It appears, though, that it involves Ca2+-dependent fusion with the lysosome membrane (Knipe and Howley 1931). **Transcription:**Transcription of the rotavirus genome is accomplished by an endogenous RNA-dependent RNA polymerase made of a complex of VP1 and VP3 found at each of the 5-fold axes of the inner core. In the triple layered particles, which have all three capsids, the transcriptase complex is inactivated, but removal of the outer capsid activates this complex. Transcription proceeds using the negative strand as a template to make positive sense RNA transcripts (capped but not poly adenylated), which are released through the channels in the capsid (Knipe and Howley 1932). **Translation:**VP4 and VP7 are both assembled on the rough endoplasmic reticulum, whereas the other viral proteins are synthesized on free ribosomes (Knipe and Howley 1932-3). **Replication:**Creation of dsRNA occurs in aggregations of subviral particles in inclusion bodies called viroplasms. Positive sense single-stranded RNA is the template for synthesis of its negative sense complement. During the entire process, the newly synthesized dsRNA remains within the partially uncoated virions in which they were produced. Interestingly, it appears that there are separate transcripts that are used for replication and translation (Knipe and Howley 1933). **Encapsidation:**Although the mechanism by which encapsidation of each—and only one of each—segment occurs is unclear, several hypotheses have been advanced. The first holds that polymerase/replication intermediates serve as nucleation sites for the formation of the inner core. A second model maintains that mRNAs are inserted into ready-made cores. The last one claims that VP1, VP3, and two copies of VP2 form tetramers, each responsible for transcribing a specific segment of the genome. After transcription of the segments, interactions between the nascent nucleic acids drives assembly of the icosahedron (Knipe and Howley 1935). **Virion Assembly:**Although subviral particles are formed in viroplasms, they end up budding through the endoplasmic reticulum, transiently giving maturing particles an envelope, a step not seen in any other viral family let alone any other genus of //Reoviridae// (Knipe and Howley 1935). Eventually, the envelope is replaced by the outermost capsid. One important viral protein in the assembly process is NSP4, which is a membrane bound protein assembled on the endoplasmic reticulum facilitating budding of the double-layered particles its lumen. In addition, this protein is thought to be involved in removal of the transient envelope by upregulating the intracellular concentration of calcium ions (Knipe and Howley 1936-7). **Egress:**Assembled virions leave cells by permeablizing the cellular membrane, resulting in cell lysis (Knipe and Howley 1938).