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===Mutation rates=== RNA viruses generally have very high [[mutation]] rates compared to [[DNA virus]]es,<ref name="SanjuanNebot2010">{{cite journal | vauthors = SanjuΓ‘n R, Nebot MR, Chirico N, Mansky LM, Belshaw R | title = Viral mutation rates | journal = Journal of Virology | volume = 84 | issue = 19 | pages = 9733β48 | date = October 2010 | pmid = 20660197 | pmc = 2937809 | doi = 10.1128/JVI.00694-10 }}</ref> because viral [[RNA-dependent RNA polymerase|RNA polymerases]] lack the [[Proofreading (biology)|proofreading]] ability of [[DNA polymerase]]s.<ref name=Klein>{{cite book | last1 = Klein | first1 = Donald W. | last2 =Prescott | first2 = Lansing M. | last3 = Harley | first3 = John | name-list-style = vanc |title=Microbiology |publisher=Wm. C. Brown |location=Dubuque, Iowa |year=1993 |isbn=978-0-697-01372-9 }}</ref> The [[genetic diversity]] of RNA viruses is one reason why it is difficult to make effective [[vaccines]] against them.<ref name="pmid3318675">{{cite journal | vauthors = Steinhauer DA, Holland JJ | title = Rapid evolution of RNA viruses | journal = Annual Review of Microbiology | volume = 41 | pages = 409β33 | year = 1987 | pmid = 3318675 | doi = 10.1146/annurev.mi.41.100187.002205 }}</ref> Retroviruses also have a high mutation rate even though their DNA intermediate integrates into the host genome (and is thus subject to host DNA proofreading once integrated), because errors during reverse transcription are embedded into both strands of DNA before integration.<ref name="pmid20846038">{{cite journal | vauthors = Boutwell CL, Rolland MM, Herbeck JT, Mullins JI, Allen TM | title = Viral evolution and escape during acute HIV-1 infection | journal = The Journal of Infectious Diseases | volume = 202 | issue = Suppl 2 | pages = S309β14 | date = October 2010 | pmid = 20846038 | pmc = 2945609 | doi = 10.1086/655653 }}</ref> Some genes of RNA virus are important to the viral replication cycles and mutations are not tolerated. For example, the region of the [[hepatitis C virus]] genome that encodes the core protein is [[conserved sequence|highly conserved]],<ref name="pmid8058787">{{cite journal | vauthors = Bukh J, Purcell RH, Miller RH | title = Sequence analysis of the core gene of 14 hepatitis C virus genotypes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 17 | pages = 8239β43 | date = August 1994 | pmid = 8058787 | pmc = 44581 | doi = 10.1073/pnas.91.17.8239 | bibcode = 1994PNAS...91.8239B | doi-access = free }}</ref> because it contains an RNA structure involved in an [[internal ribosome entry site]].<ref name="pmid15448367">{{cite journal | vauthors = Tuplin A, Evans DJ, Simmonds P | title = Detailed mapping of RNA secondary structures in core and NS5B-encoding region sequences of hepatitis C virus by RNase cleavage and novel bioinformatic prediction methods | journal = The Journal of General Virology | volume = 85 | issue = Pt 10 | pages = 3037β47 | date = October 2004 | pmid = 15448367 | doi = 10.1099/vir.0.80141-0 | doi-access = free }}</ref>
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