Model virus

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As a model virus in the will Virology , Hygiene and molecular biology , a type of virus then referred to when it is used as a prototype for a group of viruses, or as a substitute for another, experimentally very difficult to access virus. Often, non-human viruses are used as model viruses, which are very similar to the actual human virus. These non-human model viruses are but for example in an animal model , in cell culture or for reasons of biological safety more accessible or (in human viruses that were not in vitro can be propagated) compared with the human virus be cultured and laboratory capable of reproduction .

Model viruses for testing virus inactivation

To check the effectiveness of various virus inactivation and disinfection methods, it is crucial that the virus to be tested can be grown in cell culture or another method for determining infectivity (entry assay, infectivity in animal experiments) is possible. The infectivity of a defined virus preparation without using the inactivation process is compared with that after the application. A determination of the virus concentration with a quantitative PCR is not meaningful for this test, since the infectiousness of the viruses can be eliminated, for example, by denaturing the virus proteins on the virus surface or by destroying the virus envelope , but the viral nucleic acid can still be detected. Detection of the nucleic acid is not proof of the infectivity of a sample or the presence of intact viruses that are capable of replication.

Some human viruses, which are of great interest in virus inactivation of blood products or in disinfection, cannot be propagated in cell culture; they are replaced by model viruses (also referred to here as test virus , test virus or surrogate virus ) during the inactivation test. These include the human noroviruses (model virus is the murine norovirus , the feline calicivirus or the tulane virus ), the hepatitis C virus (model virus bovine virus diarrhea virus BVDV), the hepatitis B virus (model viruses Woodchuck's hepatitis virus WHV or duck hepatitis B virus DHBV), the hepatitis E virus can only multiply to a very limited extent (model viruses various reoviruses ). An example that although testing in a cell culture is possible, but increased safety measures in the laboratory make testing more difficult is the SARS coronavirus , which can be represented by the bovine coronavirus or the human coronavirus 229E .

In the case of inactivation tests that are carried out in a standardized manner, the test viruses represent entire virus groups ( DNA viruses / RNA viruses , enveloped / uncovered, lipophilic / hydrophilic ) with similar properties with regard to chemical or thermal inactivation. According to the recommendations of the German Association for Combating Viral Diseases (DVV) and the RKI , these are the vaccinia virus Elstree strain or modified vaccinia virus strain Ankara for testing limited virucidal properties (enveloped viruses), the human adenovirus type 5 (strain adenoid 75 ATCCVR-5) and the poliovirus type 1 vaccine strain LSc-2ab for testing virucidal activity in non-enveloped viruses, and the very stable bovine parvovirus for testing thermal-chemical inactivation. According to EU standard EN 14476: 2009-04, only the poliovirus type 1 vaccine strain LSc-2ab, the adenovirus type 5 and the bovine parvovirus are used.

However, the informative value of model viruses in the virucidal test is limited. Thus, the murine norovirus is considerably more environmentally unstable than the human norovirus, so that an inactivation process that shows virucidal properties with the former does not necessarily mean that human noroviruses are sufficiently virucidal. Different test viruses for the same question can come to different conclusions here.

Model viruses in virological research

In basic virological research, model viruses are used to simulate human infections in animal models, to investigate defense mechanisms against viral infections or to investigate molecular mechanisms in cell culture. Sun has long been the Bovine viral diarrhea virus BVDV a model virus for hepatitis C virus (with the only other apes can be infected and in cell culture is not culturable). The lymphocytic choriomeningitis virus (LCMV) is a classic model virus for researching the T-cellular immune defense, as is the ectromelia virus for exanthematic virus infections. The herpes virus saimiri , the Friend leukemia virus (F-MuLV) and the Simian virus 40 are model viruses for investigating the development of cancer in oncoviruses .

literature

  • I. Schwebke, HF Rabenau: Current status of the virucidal test - an overview. Hyg. Med. (2012) 37 (7/8): pp. 291–295 ( full text PDF )
  • OJ Bos et al. : Virus validation of pH 4-treated human immunoglobulin products produced by the Cohn fractionation process. Biologicals (1998) 26 (4): pp. 267-276, PMID 10403030
  • F. Käsermann et al. : Strengths and limitations of the model virus concept. PDA J. Pharm. Sci. Technol. (2004) 58 (5): pp. 244-249, PMID 15568644

See also

Individual evidence

  1. ↑ H. Rabenau et al .: Guideline of the German Association for Combating Virus Diseases (DVV) eV and the Robert Koch Institute (RKI) for testing chemical disinfectants for effectiveness against viruses in human medicine. Version dated December 1, 2014 Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz (2015) 58 (4-5): P. 493-504 PMID 25893886 ( full text as pdf)
  2. ↑ EN 14476: Chemical disinfectants and antiseptics. Virucidal quantitative suspension test for chemical disinfectants and antiseptics used in Human Medicine from May 12, 2005, amendment April 2009
  3. ↑ T. Cromeans et al .: Comprehensive comparison of cultivable norovirus surrogates in response to different inactivation and disinfection treatments. Appl. Environ. Microbiol. (2014) 80 (18): pp. 5743-5751 PMID 25015883