Human adenoviruses

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Human adenoviruses
Adenovirus transmission electron micrograph B82-0142 lores.jpg

Adenoviruses in the TEM

Systematics
Classification : Viruses
Area : Varidnaviria
Empire : Bamfordvirae
Phylum : Preplasmiviricota
Class : Tectiliviricetes
Order : Rowavirales
Family : Adenoviridae
Genre : Mastadenovirus
Type : Human mastadenovirus AG
Taxonomic characteristics
Genome : dsDNA linear
Baltimore : Group 1
Symmetry : icosahedral
Cover : no
Scientific name
Human mastadenovirus AG
Short name
HAdV
Left
NCBI  Taxonomy: 10508 (family)
ICTV Taxon History: 201852424 (HAdV-C)
ICTVdB Virus Code : 00.001

Human adenoviruses (HAdV) are human pathogenic viruses from the family Adenoviridae and the genus Mastadenovirus . Seven of the 45 species of this genus (as of the International Committee on Taxonomy of Viruses (ICTV), November 2018) can cause diseases in humans and were first detected in 1953 by Wallace P. Rowe and others as pathogens for respiratory infections and from human tonsils (adenoids) isolated, from which its name is derived. (These viruses and other Adenoviridae, which cause necrotic changes in adenoid tissue in culture, were formerly also known as AD agents , from English Adenoid Degeneration Agents .) At present, over 50 serologically distinguishable subtypes have been identified.

features

Adenoviruses which are pathogenic to humans belong to the group of non - enveloped, double-stranded, linear DNA viruses (dsDNA), which is why they are characterized by their high stability against chemical and physical influences and tolerate extreme pH values ​​and alcoholic disinfectants . On the other hand, heating them for ten minutes to 56 ° C completely inactivates them. Their stable icosahedral capsid and the lack of a sensitive shell lead to long-lasting infectivity outside the host body . HAdVs have a diameter of around 70–90  nm . The size of the genome is with 26 to 45 kilobase pairs in the middle range of the DNA viruses.

  • Adenovirus virion

  • Structure of the adenoviruses

  • Scheme drawing of an adenovirus

  • Adenovirus genome

clinic

Adenoviruses mainly cause respiratory diseases . Depending on the respective serotype , a number of other diseases can also be caused, such as gastroenteritis , epidemic keratoconjunctivitis , cystitis , rhinitis , pharyngitis or diarrhea . The symptoms of adenovirus respiratory disease range from the common cold to acute bronchitis and pneumonia . Patients with a weakened immune system are particularly susceptible to serious complications from adenovirus infections, such as Acute Respiratory Distress Syndrome ( ARDS ). It is also believed that there is a link between the Ad-36 virus type and obesity in humans.

Epidemiology

Although the epidemiological characteristics of adenoviruses vary from type to type, they are all passed through direct contact, fecal - oral and occasionally waterborne transmission. Some species cause persistent, asymptomatic infections of the tonsils, tonsils, or gastrointestinal tract of the host; it can spread over months or years. Few adenoviruses ( e.g., serotypes 1, 2, 5 and 6: human mastadenovirus C , HAdV-2) have been shown to be endemic to some areas of the world ; the infection usually already occurs in childhood. Other species cause occasional outbreaks in otherwise sporadic infections. For example, epidemic keratoconjunctivitis is triggered by serotypes 8, 19 and 37 ( human mastadenovirus D , HAdV-9). Epidemic occurring febrile disease with conjunctivitis are often associated with adenoviruses and occur insufficiently chlorinated swimming pools and small lakes on generally in the environment. Gastroenteritis is caused, especially in children, by serotypes 40 and 41 ( human mastadenovirus F , HAdV-40). For some serotypes, the clinical spectrum of infection-associated diseases varies depending on the portal of entry. For example, an infection with serotype 7 ( human mastadenovirus B , HAdV-3) by inhalation is associated with serious diseases of the lower respiratory tract, while oral transmission of the virus causes no or only a mild infection.

diagnosis

Antigen detection, PCR assay, virus isolation, electron microscopy and serology are used to detect adenovirus infections. The type determination is usually carried out by means of a hemagglutination inhibition reaction or neutralization with type-specific antisera . Since adenoviruses can be excreted over a longer period of time, the detection of the virus does not necessarily mean the detection of a disease.

therapy

Most infections are mild and do not require therapy or symptomatic treatment. But even in the case of serious illnesses caused by adenovirus infections, treatment is directed towards the symptoms and complications of the infection in the absence of virus-specific therapy.

Prevention

Adenovirus vaccines have been developed for serotypes 4 and 7, but these are only available for the prevention of severe respiratory infections in recruits to the US armed forces. Careful infection control is necessary to effectively limit the spread of adenovirus-associated diseases, such as epidemic keratoconjunctivitis , which caused the temporary closure of several Bundeswehr bases in 2004 .

Late complications

Various clinical pictures are discussed that can appear as late effects of an adenovirus infection, such as persistent bronchiolitis , joint pain, dilated cardiomyopathy or sudden hearing loss . It has often been assumed up to now that adenoviruses were also considered to be the trigger for type 1 diabetes , but this turned out to be relatively unlikely due to the results of the international TEDDY study ( The Environmental Determinants of Diabetes in the Young ).

Therapeutic use of adenoviruses in medicine

Human adenoviruses (especially type 5 from species C) are a gene therapy vector that is widely used in laboratories. They are increasingly being used in medical therapy. Examples:

research

  • Gene therapy for complete color blindness ( achromatopsia ) caused by a defective CNGA3 gene . A team at Tübingen University Hospital has been testing since 2020 how adenoviruses can be used as a vector for a functional version of the gene (then referred to as the AAV8.CNGA3 gene ). Given the right conditions, there is a good chance of success, especially with young patients.
  • Above all, adenoviral vectors are to be used increasingly in cancer therapy in the future.

Reporting requirement

The obligation to report adenoviruses only from conjunctival smears is subject to Section 7 IfSG in Germany .

Web links

Individual evidence

  1. ↑ a b c d e ICTV: ICTV Taxonomy history: Human mastadenovirus C , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  2. ↑ Werner Köhler : Infectious diseases. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , pp. 667-671; here: p. 671.
  3. ↑ Hans von Kress (ed.): Müller - Seifert . Pocket book of medical-clinical diagnostics. 69th edition. Bergmann-Verlag, Munich 1966, p. 1069.
  4. ^ Andrew J. Davison, Mária Benkő, Balázs Harrach: Genetic content and evolution of adenoviruses . In: Journal of General Virology . tape 84 , no. 11 , 2003, p. 2895–2908 , doi : 10.1099 / vir.0.19497-0 ( microbiologyresearch.org [accessed November 1, 2017]).
  5. ↑ H.-S. Lee et al .: Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes. In: Diabetologia. August 2013, Volume 56, No. 8, pp. 1705–1711, doi: 10.1007 / s00125-013-2924-y , ( link.springer.com full text as PDF).
  6. ↑ Jana Zeh: Safe virus as carrier - vaccine from China shows immune reactions . On: n-tv.de from May 26, 2020.
  7. ↑ Feng-Cai Zhu, Yu-Hua Li, Xu-Hua Guan, Li-Hua Hou, Wen-Juan Wang, Jing-Xin Li et al. : Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomized, first-in-human trial . In: The Lancet. May 22, 2020, doi: 10.1016 / S0140-6736 (20) 31208-3 .
  8. ↑ H. Tazawa, S. Kagawa, T. Fujiwara: Advances in adenovirus-mediated p53 cancer gene therapy. In: Expert opinion on biological therapy. Volume 13, Number 11, November 2013, ISSN  1744-7682 , pp. 1569-1583, doi: 10.1517 / 14712598.2013.845662 , PMID 24107178 .
  9. ↑ Nadja Podbregar: First gene therapy against complete color blindness , on: scinexx.de from May 7, 2020.
  10. ↑ M. Dominik Fischer, Stylianos Michalakis, Barbara Wilhelm, et al. : Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia . In: JAMA Ophthalmology. Volume 138, No. 6, April 30, 2020, pp. 643-651, doi: 10.1001 / jamaophthalmol.2020.1032 .
  11. ↑ juris: IfsG §7 , accessed on December 11, 2018.