Rhinovirus

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Rhinovirus
Rhinovirus isosurface.png

Illustration of rhinovirus 14

Systematics
Classification : Viruses
Area : Riboviria
Empire : Orthornavirae
Phylum : Pisuviricota
Class : Pisoniviricetes
Order : Picornavirales
Family : Picornaviridae
Genre : Enterovirus
Type : Rhinovirus A , B , C , Enterovirus D
Taxonomic characteristics
Genome : (+) ssRNA linear
Baltimore : Group 4
Symmetry : icosahedral
Cover : no
Scientific name
Rhinovirus
Short name
HRV-A, HRV-B, HRV-C; HRV-87
Left
NCBI  Taxonomy: 147711 (HRV-A) ,
147712 (HRV-B) ,
463676 (HRV-C) ;
167331 (HRV-87)
ICTV Taxon History: 201851993 (HRV-A) ,
201851994 (HRV-B) ,
201851995 (HRV-C) ;
201851986 (HRV-87)
ICTVdB Virus Code : 00.052.0.02

The rhinovirus is a pathogen that is primarily responsible for runny nose and colds . Rhinoviruses belong to the enterovirus genus of the family Picornaviridae in the order Picornavirales (name of pico , i.e. small and RNA ) and form three species (species) rhinovirus A – C (formerly also called human rhinovirus A – C ). Over 100 serotypes have been described. According to the NCBI, HRV-87 is a subtype of Enterovirus D ; the NCBI also lists a number of other unclassified rhinoviruses.

construction

Virion

Due to their homology , rhinoviruses are divided into three groups (A to C). Rhinoviruses are not enveloped , which means that they do not have a lipid layer as an envelope. Their diameter is between 24 nm and 30 nm and therefore they belong to the small viruses (150 S in a density gradient centrifugation ). Compared to the closely related enteroviruses, they are relatively acid-sensitive and therefore not gastric juice- resistant, but more thermostable , have a narrower host tropism and narrower replication conditions (only lower temperatures and not in the intestinal tissue). Each capsid protein occurs 60 times in the icosahedral capsid of the virion with a cubic symmetrical structure. In the middle of each of the 20 surfaces of the capsid is a depression ( canyon , gorge) for binding the receptor. The capsid has a layer thickness of about 5 nm. About 90% of the strains of species A and B use ICAM-1 as the cellular receptor , the remaining 10% use the LDL receptor . The strains of species C use a previously unknown cellular receptor.

Genome

Rhinoviruses are RNA viruses with single stranded RNA - genome of positive polarity of approximately 7.2 to 8.5  kilobases in length. The viral proteins are produced as polyproteins of about 2200 amino acids and then split into the individual proteins by two proteases (encoded by the two pro genes 2Apro and 3Cpro) . The structural proteins in the virion are encoded in the 5 'area of the RNA, the non-structural proteins in the 3' area (as in all picornaviruses). At the 5 'end is a 5' UTR , followed by the regions P1 ( Gene 1A-D for the four capsid proteins VP1-4), P2 (Gene 2Apro, 2B, 2C), P3 (3A, 3B, 3Cpro, 3Dpol for the VPg, the protease and the RNA polymerase ), the 3 'UTR (redundant in a cell culture ) and a poly-A tail . The 5 'end of the viral RNA is linked to the viral protein VPg .

Proteins

Like all picornaviruses, rhinoviruses have four capsid proteins (VP1 to VP4) which, in addition to packaging the genome, sometimes also serve as receptors for attachment to a cell. The VP4 connects the proteins VP1, VP2 and VP3, which are external to the virion, with the genome. As surface proteins, VP1-3 are increasingly recognized by antibodies . After binding of the cellular receptor, the N-terminus of VP1 is turned outward from the virion and the VP4 is released, which together form a pore for penetrating the cell membrane through which the viral RNA is channeled into the cytosol . Protein 2Apro is a cysteine ​​protease used to cleave the polyprotein between the P1 and P2 regions. Protein 2B serves to destabilize the cell membrane to facilitate the release of newly formed virions from the cell. Protein 2C has a previously unknown function. Protein 3A is a membrane protein that binds the newly formed virions to the cell membrane for easier release. Protein 3B (syn. VPg , viral protein on the genome) binds to the 5 'end of the viral RNA and has previously unknown functions. Protein 3Cpro is a cysteine ​​protease that cleaves the cellular proteins Nup153 , Nup214 and Nup358 and thereby interrupts the release of molecules from the cell nucleus . Protein 3DPol is an RNA polymerase used to replicate viral RNA. The proteins VP1-4 and VPg occur in the virion and are therefore referred to as structural proteins.

Replication cycle

After binding to the respective receptor, the cell membrane is penetrated by the pore-forming proteins VP1 and VP4, where the viral polyprotein is produced from the viral RNA on the ribosomes . The replication of the viral RNA takes place after a transfer into the smooth endoplasmic reticulum (ER) by the RNA polymerase 3DPol. The copied genomes are channeled from the endoplasmic reticulum into the cytosol, where the viral RNA and the viral proteins combine to form virions. Rhinoviruses are lytic viruses and leave the host cell by destroying them.

Occurrence

Rhinoviruses are widespread worldwide and are limited to humans, but prefer temperatures of 3 ° C to 33 ° C, which they absolutely need for their reproduction. At higher temperatures - e.g. B. at body temperature (36 ° C to 37.5 ° C) - their reproduction is inhibited. This preference for slightly cooler temperatures causes the higher infection rate in wet and cold weather and the tropism for the cooler nasal mucosa . Since the blood vessels in the nasal mucous membrane contract when the body is cold, the temperature of the nasal mucous membrane drops to the area that is optimal for these viruses.

infection

Routes of infection

Rarely, the infection occurs through the transmission of viruses in droplets of various body fluids, which are expelled by already infected people when they sneeze or cough and are then transmitted to another person via droplet infection , since the rhinoviruses in dry air by drying in a few minutes be inactivated. In 80% moist, 20 ° C warm air, they remain active for hours ( half-life 14  h ); However, since the larger droplets quickly sink to the ground, the virus concentration in the air drops quickly after a sneeze. Far more common is direct transmission, e.g. B. via contaminated hands, or indirectly via objects ( smear infection ). People whose immune system has been weakened or - as is the case with babies and toddlers - not yet trained against the over 100 different rhinoviruses are particularly often infected.

incubation period

The incubation period is relatively short. Viruses can be detected in the nose after one to four days, after which viruses are produced for two to three days until the adaptive immune response intervenes. After about 12 hours, the first finished viruses leave the host cell and infect the next.

Infection symptoms

Rhinoviruses infect the mucous membranes of the nose and throat, remain strictly localized and do not cause generalized infection. A runny nose develops - bronchitis is less common in children . The human body reacts to the virus attacks with an inflammatory reaction of the nasal mucous membrane. The vessels of the mucous membrane become more permeable, fluid escapes, the nose runs. Later the nasal mucous membrane swells up to half a centimeter thick, which makes breathing through the nose almost impossible. In addition, there may be malaise and headaches. In addition to the viral infection, a secondary infection by bacteria often occurs in the throat and pharynx.

Therapy and Prevention

Capsid protein VP1 (in green) with pleconaril

Specific antiviral therapy is not available, nor is immunoprophylaxis (vaccination). In the case of immunocompetent people, this is also not necessary, since neither permanent damage nor severe courses are observed. Treatment of the disease is limited to treating the symptoms until the virus has been eliminated by the immune system and the symptoms of inflammation have subsided.

Various vaccines were produced in the 1960s, but they could only produce strain-specific vaccination protection. A rhinovirus infection also leads to the development of neutralizing antibodies , which, however, only produce strain-specific immunity . As RNA viruses, rhinoviruses tend to mutate more intensely in the course of immune evasion and the capsid proteins of four typical rhinovirus strains are only between 41 and 83% identical to one another, which makes it difficult to develop cross-strain immunity. In people who have already had multiple infections from different strains, the duration of the illness is somewhat shorter.

Prevention is possible through exposure prophylaxis (e.g. avoiding crowds and hand washing), because long-term drugs or vaccines cannot be produced due to the large number of serotypes and only type-specific immunity. In addition, the antiviral Pleconaril prevents the unpacking of the viral genome of non-resistant rhinoviruses.

Environmental stability

As picornaviruses, rhinoviruses have a relatively high tenacity compared to other viruses , but unlike the related enteroviruses, they are sensitive to acids. The tenacity of rhinoviruses includes a relatively high resistance to alcohols (e.g. ethanol , isopropanol ) and surfactants due to the lack of a virus envelope , but most of them can be removed from hands by washing hands. Rhinoviruses are sensitive to acids , alkylating agents and physical disinfection methods .

Individual evidence

  1. ↑ ICTV Master Species List 2018b.v2 . MSL # 34, March 2019
  2. ↑ a b c d ICTV: ICTV Taxonomy history: Enterovirus C , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  3. ↑ a b c J. L. Kennedy, RB Turner, T. Braciale, PW Heymann, L. Borish: Pathogenesis of rhinovirus infection. In: Current opinion in virology. Volume 2, Number 3, June 2012, ISSN  1879-6265 , pp. 287-293, doi : 10.1016 / j.coviro.2012.03.008 , PMID 22542099 . PMC 3378761 (free full text).
  4. ^ SE Jacobs, DM Lamson, K. St. George, TJ Walsh: Human Rhinoviruses. In: Clinical Microbiology Reviews. Volume 26, number 1, January 2013, ISSN  0893-8512 , pp. 135-162, doi : 10.1128 / CMR.00077-12 , PMID 23297263 , PMC 3553670 (free full text).
  5. ↑ ICTV : Master Species List 2018a v1 , MSL including all taxa updates since the 2017 release. Fall 2018 (MSL # 33)
  6. ↑ ViralZone: ICTV 2016 Master Species List # 31 with Acronyms, (Excel XLSX) , SIB Swiss Institute of Bioinformatics
  7. ↑ YA Bochkov, AC Palmenberg, WM Lee, JA Rathe, SP Amineva, X. Sun, TR Pasic, NN Jarjour, SB Liggett, JE Gern: Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. In: Nature Medicine . Volume 17, number 5, May 2011, ISSN  1546-170X , pp. 627-632, doi : 10.1038 / nm.2358 , PMID 21483405 , PMC 3089712 (free full text).
  8. ↑ a b c d e f D. M. Knipe, Peter M. Howley , DE Griffin, (Ed.): Fields Virology. (two volumes) 5th edition, Lippincott Williams & Wilkins, Philadelphia 2007, ISBN 978-0-7817-6060-7 .
  9. ^ Robert B Couch: Rhinoviruses: Replication . In: Anne O'Daly (Ed.): Encyclopedia of Life Sciences . John Wiley, 2005, ISBN 0-470-01590-X .
  10. ↑ M. Rossmann, E. Arnold, J. Erickson, E. Frankenberger, J. Griffith, H. Hecht, J. Johnson, G. Kamer, M. Luo, A. Mosser: Structure of a human common cold virus and functional relationship to other picornaviruses . In: Nature . 317, No. 6033, 1985, pp. 145-153. bibcode : 1985Natur.317..145R . doi : 10.1038 / 317145a0 . PMID 2993920 .
  11. ↑ T. Smith, M. Kremer, M. Luo, G. Vriend, E. Arnold, G. Kamer, M. Rossmann, M. McKinlay, G. Diana, M. Otto: The site of attachment in Human rhinovirus 14 for antiviral agents that inhibit uncoating . In: Science . 233, No. 4770, 1986, pp. 1286-1293. bibcode : 1986Sci ... 233.1286S . doi : 10.1126 / science.3018924 . PMID 3018924 .
  12. ↑ a b c d e Uniprot P03303.
  13. ^ YG Karim, MK Ijaz, SA Sattar, CM Johnson-Lussenburg: Effect of relative humidity on the airborne survival of rhinovirus-14. In: Canadian journal of microbiology. Volume 31, Number 11, November 1985, ISSN  0008-4166 , pp. 1058-1061, PMID 3004682 .
  14. ↑ M. Schmidtke, P. Wutzler, R. Zieger WHETHER Riabova, VA Makarov: New pleconaril and [(biphenyloxy) propyl] isoxazole derivatives with substitutions in the central ring exhibit antiviral activity against pleconaril-resistant coxsackievirus B3. In: Antiviral Research . Volume 81, Number 1, January 2009, ISSN  1872-9096 , pp. 56-63, doi : 10.1016 / j.antiviral.2008.09.002 , PMID 18840470 .
  15. ↑ a b C. Savolainen-Kopra, T. Korpela, ML Simonen-Tikka, A. Amiryousefi, T. Ziegler, M. Roivainen, T. Hovi: Single treatment with ethanol hand rub is ineffective against human rhinovirus - hand washing with soap and water removes the virus efficiently. In: Journal of medical virology. Volume 84, Number 3, March 2012, ISSN  1096-9071 , pp. 543-547, doi : 10.1002 / jmv.23222 . PMID 22246844 .
  16. ↑ RB Turner, KA Biedermann, JM Morgan, B. Keswick, KD Ertel, MF Barker: Efficacy of organic acids in hand cleansers for prevention of rhinovirus infections. In: Antimicrobial Agents and Chemotherapy . Volume 48, Number 7, July 2004, ISSN  0066-4804 , pp. 2595-2598, doi : 10.1128 / AAC.48.7.2595-2598.2004 , PMID 15215114 , PMC 434190 (free full text).
  17. ↑ RB Turner, JO Hendley: Virucidal hand treatments for prevention of rhinovirus infection. In: Journal of Antimicrobial Chemotherapy . Volume 56, Number 5, November 2005, ISSN  0305-7453 , pp. 805-807, doi : 10.1093 / jac / dki329 , PMID 16159927 .
  18. ↑ K. Broo, J. Wei, D. Marshall, F. Brown, TJ Smith, JE Johnson, A. Schneemann, G. Siuzdak: Viral capsid mobility: a dynamic conduit for inactivation. In: Proceedings of the National Academy of Sciences of the United States of America . Volume 98, Number 5, February 2001, ISSN  0027-8424 , pp. 2274-2277, doi : 10.1073 / pnas.051598298 , PMID 11226229 , PMC 30128 (free full text).

literature

  • Samantha E. Jacobs, Daryl M. Lamson, Kirsten St. George, Thomas J. Walsh: Human Rhinoviruses. In: Clinical Microbiology Reviews. Volume 26, number 1, January 2013, ISSN  0893-8512 , pp. 135-162, doi : 10.1128 / CMR.00077-12 , PMID 23297263 , PMC 3553670 (free full text).
  • Ian M. Mackay, Katherine E. Arden: Rhinoviruses. In: Richard A. Kaslow, Lawrence R. Stanberry, James W. Le Duc (Eds.): Viral Infections of Humans. 5th edition. Springer, New York 2014, ISBN 978-1-4899-7447-1 , pp. 675-712.
  • Ronald B. Turner: Rhinovirus. In: John E. Bennett, Raphael Dolin, Martin J. Blaser (Eds.): Principles and Practice of Infectious Diseases. Vol. 2, 8th edition. Elsevier Saunders, Philadelphia 2015, ISBN 9780443068393 , pp. 2113-2121.

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