Editing Serial passage (section)

===Increasing virulence for use in animal modeling===
When developing vaccines for viruses, the emphasis is on attenuating the virus, or decreasing its virulence, in a given host.  Sometimes it is useful to employ serial passage to increase the virulence of a virus.  Usually, when serial passage is performed in a species, the result is a virus that is more virulent to that species.<ref name = woo/>

For example, one study<ref name="locher">{{Cite journal |vauthors=Locher CP, Witt SA, Herndier BG, Abbey NW, Tenner-Racz K, Racz P, Kiviat NB, Murthy KK, Brasky K, Leland M, Levy JA |date=January 2003 |title=Increased virus replication and virulence after serial passage of human immunodeficiency virus type 2 in baboons |journal=Journal of Virology |volume=77 |issue=1 |pages=77–83 |doi=10.1128/jvi.77.1.77-83.2003 |pmc=140565 |pmid=12477812}}</ref> used serial passage in baboons to create a strain of HIV-2 that is particularly virulent to baboons.  Typical strains of HIV-2 only infect baboons slowly.<ref name=locher/>  This specificity makes it challenging for scientists to use HIV-2 in animal models of HIV-1, because the animals in the model will only show symptoms slowly. The more virulent strain of HIV-2 could be practical for use in animal models, however.<ref name=locher/>

Another study by Kanta Subbaro involved a serial passage experiment in which mice were infected with [[SARS]].<ref name="zimmer">{{Cite book |last=Zimmer |first=Carl |title=The Tangled Bank |date=2013 |publisher=Robert and Co. Publishers |edition=second |pages=399–427 |chapter=Chapter 15}}</ref>  SARS usually does not make mice particularly sick, however, after the virus had undergone serial passage in the mice, it had become lethal.<ref name="zimmer" />

Changing the virulence of SARS in this way was important, because without a virulent form of SARS to infect laboratory animals, scientists would have been unable to test the effects of SARS in an animal model.<ref name="zimmer" />

More generally, this experiment also reflects a general medical principle: The virulence of a virus is mediated by the difficulty of its transmission.

Generally, if a virus kills its host too quickly, the host will not have a chance to come in contact with other hosts and transmit the virus before dying.  In serial passage, when a virus was being transmitted from host to host regardless of its virulence, such as Subbaro's experiment, the viruses that grow the fastest (and are therefore the most virulent) are selected for.<ref name="zimmer" />

This principle has public health implications, because it suggests that, in very densely populated or overcrowded areas, such as slums or [[Pest house|group quarantine facilities]], natural selection may favour more virulent viruses.

This also helps explain why good hygiene is so important. Good hygiene selects against highly virulent viruses by lowering the ability of pathogens to transmit.<ref name="zimmer" />

Serial passaging has been used to produce mouse-adapted SARS-CoV-2.<ref name="pandey">{{Cite journal |last1=Pandey |first1=Kabita |last2=Acharya |first2=Arpan |year=2021 |title=Animal models for SARS-CoV-2 research: A comprehensive literature review |journal=Transboundary and Emerging Diseases |publication-date=October 2020 |volume=68 |issue=4 |pages=1868–1885 |doi=10.1111/tbed.13907 |pmc=8085186 |pmid=33128861}}</ref><ref>{{cite journal|vauthors=Gu H, Chen Q, Yang G, He L, Fan H, Deng YQ, Wang Y, Teng Y, Zhao Z, Cui Y, Li Y, Li XF, Li J, Zhang NN, Yang X, Chen S, Guo Y, Zhao G, Wang X, Luo DY, Wang H, Yang X, Li Y, Han G, He Y, Zhou X, Geng S, Sheng X, Jiang S, Sun S, Qin CF, Zhou Y|title=Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy|journal=Science|volume=369|issue=6511|pages=1603–1607|date=25 September 2020|pmid=32732280|pmc=7574913|doi=10.1126/science.abc4730}}</ref>