Adaptation to Cultured Cells or Laboratory Animals

Major advances in the understanding of viruses involved in human disease usually depend on being able to grow them in cultured cells or in a laboratory animal Most wild-type viruses initially grow poorly in cell culture or laboratory animals, but they can be "adapted" to their new host by serial passage of high-titer inocula Such adaptation depends on the spontaneous generation of mutations and progressive selection of the best growing mutant. These host range mutants may contain mutations in any of several genes, often in that encoding the surface protein which binds the somewhat different type of receptor available on the new host cell. For example, influenza virus may acquire the capacity to grow well m the lungs of mice or in cultured cell lines via a point mutation affecting either the ligand of (he hemagglutinin (HA) molecule that engages (he cell receptor, or Ihe site of proteolytic cleavage of the HA that is essential for uncoating of the endocytosed virion. The mutation may occur within either of these two critical sites, or within a nearby glyco-sylation sequence (Asn-X-Val/Thr), thereby exposing a site that would otherwise be obstructed by an oligosaccharide side chain.

Some viruses produce clinical signs of disease the first time that they are inoculated into an experimental animal, for instance, eastern equine encepha litis virus in suckling mice In oilier cases minimal signs of infection are observed initially, but after serial passage, sometimes piolonged, clinical disease is regularly produced, as, for example, in the adaptation of pohovirus to mice Likewise, newly isolated viruses at fust often lail to grow in certain kinds of cultured cells, but can be adapted by serial passage Most virologic research is performed with strains of virus adapted to grow rapidly to high yield and to produce plaques or cytopathic changes in continuous cell lines. A frequent by-product of such adaptation to a new experimental host is the coincident attenuation of the virus for its original host, for example, polio-viruses, by their adaptation to monkey kidney cell cultures and serial passage in them, were attenuated sufficiently to be used as vaccines

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