Editing Rotavirus (section)

=== Replication ===
[[File:Rotavirus replication.png|thumb|A simplified drawing of the rotavirus replication cycle.<ref name="Gray Desselberger 2000 p. ">{{cite book | last1=Gray | first1=James | last2=Desselberger | first2=U. | title=Rotaviruses : methods and protocols | publisher=Humana Press | publication-place=Totowa, N.J. | date=2000 | isbn=978-1-59259-078-0 | oclc=55684328 | page=5}}</ref> The stages are:{{numbered list|Attachment of the virus to the host cells, which is mediated by VP4 and VP7|Penetration of the cell by the virus and uncoating of the viral capsid|Plus strand ssRNA synthesis (this acts as the mRNA) synthesis, which is mediated by VP1, VP3 and VP2|Formation of the viroplasm, viral RNA packaging and minus strand RNA synthesis and formation of the double-layered virus particles|Virus particle maturation and release of progeny virions}}]]

The attachment of the virus to the host cell is initiated by VP4, which attaches to molecules, called [[glycans]], on the surface of the cell.<ref name="pmid31317495"/> The virus enters cells by [[endocytosis|receptor mediated endocytosis]] and form a [[Vesicle (biology)|vesicle]] known as an [[endosome]]. Proteins in the third layer (VP7 and the VP4 spike) disrupt the membrane of the endosome, creating a difference in the [[Calcium in biology|calcium]] concentration. This causes the breakdown of VP7 [[Trimer (biochemistry)|trimers]] into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP).<ref name="pmid20397068">{{cite book |vauthors=Baker M, Prasad BV |chapter=Rotavirus cell entry |series=Current Topics in Microbiology and Immunology |title=Cell Entry by Non-Enveloped Viruses |volume=343 |pages=121–148 |year=2010 |pmid=20397068 |doi=10.1007/82_2010_34 |isbn=978-3-642-13331-2 |veditors=Johnson J}}</ref>

The eleven dsRNA strands remain within the protection of the two protein shells and the viral [[RNA replicase|RNA-dependent RNA polymerase]] creates mRNA transcripts of the double-stranded viral genome. By remaining in the core, the viral RNA evades innate host immune responses including [[RNA interference]] that are triggered by the presence of double-stranded RNA.<ref name="pmid27009959">{{cite journal |vauthors=Arnold MM |title=The Rotavirus Interferon Antagonist NSP1: Many Targets, Many Questions |journal=Journal of Virology |volume=90 |issue=11 |pages=5212–5215 |year=2016 |pmid=27009959 |pmc=4934742 |doi=10.1128/JVI.03068-15 }}</ref>

During the infection, rotaviruses produce mRNA for both [[protein biosynthesis]] and gene replication. Most of the rotavirus proteins accumulate in viroplasm, where the RNA is replicated and the DLPs are assembled. In the viroplasm the positive sense viral RNAs that are used as templates for the synthesis of viral genomic dsRNA are protected from [[siRNA]]-induced RNase degradation.<ref name="pmid15220450">{{cite journal |vauthors=Silvestri LS, Taraporewala ZF, Patton JT |title=Rotavirus replication: plus-sense templates for double-stranded RNA synthesis are made in viroplasms |journal=Journal of Virology |volume=78 |issue=14 |pages=7763–7774 |year=2004 |pmid=15220450 |pmc=434085 |doi=10.1128/JVI.78.14.7763-7774.2004 }}</ref> Viroplasm is formed around the cell nucleus as early as two hours after virus infection, and consists of viral factories thought to be made by two viral nonstructural proteins: NSP5 and NSP2. Inhibition of NSP5 by RNA interference ''in vitro'' results in a sharp decrease in rotavirus replication. The DLPs migrate to the [[endoplasmic reticulum]] where they obtain their third, outer layer (formed by VP7 and VP4). The [[Offspring|progeny]] viruses are released from the cell by [[cell lysis|lysis]].<ref name="pmid15010218" /><ref name="pmid15579070">{{cite journal |vauthors=Patton JT, Vasquez-Del Carpio R, Spencer E |title=Replication and transcription of the rotavirus genome |journal=Current Pharmaceutical Design |volume=10 |issue=30 |pages=3769–3777 |year=2004 |pmid=15579070 |doi=10.2174/1381612043382620}}</ref><ref name="pmid20024520">{{cite journal |vauthors=Ruiz MC, Leon T, Diaz Y, Michelangeli F |title=Molecular biology of rotavirus entry and replication |journal=The Scientific World Journal |volume=9|pages=1476–1497 |year=2009 |pmid=20024520 |pmc=5823125 |doi=10.1100/tsw.2009.158 |doi-access=free }}</ref>