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Chapter: Microbiology and Immunology: Virology, Virus: Miscellaneous Viruses

Coronaviruses

Coronaviruses were so named for the crown-like appearance of their virions on electron microscopy.

Coronaviruses

Coronaviruses were so named for the crown-like appearance of their virions on electron microscopy. These viruses are the second most important cause of the common cold; rhinovi-ruses being the first cause. The coronaviruses have also been reported to cause gastroenteritis in children and adults. Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is a newly described coronavirus in 2002. The virus causes an atypical pneumonia called SARS, a serious and potentially life-threatening viral infection of humans.

SARS-CoV causing atypical pneumonia called severe acute respiratory syndrome or SARS was first reported in 2002 and 2003 outbreak. This outbreak caused by the virus is believed to have originated in Guangdong province, south China. It predominantly affected mainly China, Hong Kong, Singapore, and Taiwan. Subsequently, this outbreak spread to neighboring countries in Asia, Canada, and the United States.

Properties of the Virus

 Morphology

Coronaviruses show following features:

·           Coronaviruses are enveloped viruses measuring 80–160 nm in size on electron microscopy.

·           The glycoproteins appear as club-shaped projections (20 nm long and 5–11 nm wide) on surface of the envelope.

·           The genome in association with N protein forms a helical nucleocapsid.

·           The virus contains the glycoproteins E1 and E2 and a core nucleoprotein N. Some strains also contain a glycoprotein E3, which is a hemagglutinin neuraminidase. E1 glycoprotein is a transmembrane matrix protein; E2 glycoprotein mediates viral attachment and membrane fusion.

SARS-CoV is a single-stranded, nonsegmented, plus-sense RNA virus. It measures approximately 30 kb in length. The genomic sequence of SARS-CoV is different from other corona-virus strains. These strains of SARS-CoV are quite stable unlike other coronaviruses in which mutations in the RNA sequence during replication of virus are common. Such mutations contribute to the appearance of new virus to be either more or less virulent. In contrast, the genome sequence of different isolates of SARS-CoV is very similar.

 Viral isolation

The attachment of the virus to the cell is mediated by hemag-glutinin. The virus enters the cell and uncoats. The replication of the virus occurs in cytoplasm. Synthesis of protein occurs in two stages similar to that of togaviruses. In the first stage, the viral genome is transcribed to produce an RNA-dependent RNA polymerase. Subsequently, the polymerase produces a negative-sense template RNA. This template RNA is utilized by the N protein to produce new viral genomes and individual messenger RNAs (mRNAs) encoding other viral proteins. The assembly of viruses occurs and derives its envelope from the endoplasmic reticulum but not from the plasma membrane.

 Antigenic and genomic structure

Coronaviruses have two serotypes, namely, 229E and OC43. SARS virus is relatively stable.

 Other properties

The coronaviruses are sensitive to acid, ether, and bile.

 Virus isolation

The coronaviruses are difficult to grow in routine cell cultures.

Pathogenesis and Immunity

The coronaviruses are confined strictly to the mucosal cells of the respiratory tract. These viruses typically cause infections in the upper respiratory tract, because the optimal temperature  for replication of viruses is 37–38°C. The envelope contains (a) E2 viral attachment protein, (b) E1 matrix protein, and (c) N1 nucleocapsid protein. Early phase of the infection pro-duces RNA polymerase (E); late phase produces structural and nonstructural proteins from a negative-sense RNA template.

SARS-CoV causes infection in the respiratory tract by binding to angiotensin-converting enzyme 2 receptors on the surface of respiratory epithelium. This causes alteration in fluid balance and leads to development of edema in alveolar space. Diffuse edema resulting in hypoxia is characteristic of pneumonia caused by SARS-CoV.

Infections caused by coronaviruses produce a short and brief immunity, but reinfection can occur.

Clinical Syndromes

Coronaviruses cause following syndromes: (a) common cold, (b) gastroenteritis, and (c) SARS.

 Common cold

The coronaviruses (229E and OC43) cause more commonly upper respiratory tract, and less commonly, lower respiratory tract illnesses in humans. Common cold caused by coronaviruses has an incubation period of 3 days. The condition is characterized by rhinorrhea, sore throat, and low-grade fever. The condition typically lasts for several days.

 Gastroenteritis

The coronaviruses have also been reported to cause gastroen-teritis in children and adults. The symptoms are mild, and the condition is self-limiting.

 SARS

SARS is a potentially life-threatening infection associated with the onset of flu-like syndrome, which may progress to pneumonia, respiratory failure, and in some cases death. The incubation period varies from 2 to 7 days, although it may be as long as 2 weeks.

Flu-like prodrome is the first stage of the disease, which is characterized by fever (.30°C), fatigue, chills, malaise, anorexia, and myalgia. Second stage represents the lower respiratory tract illness that begins three or more days after incubation. Hypoxia, cough, dyspnea, and breathing difficulties are common find-ings. The cough typically tends to be dry and nonproductive and may range from mild to severe. Fever is typically higher than 30°C. Chest X ray shows interstitial ground glass infil-trates that do not show cavitation. The condition is associated with lymphadenopathy and thrombocytopenia.

Morbidity and mortality due to SARS is more in elderly population and also seen in more individuals with coexisting chronic illness and immunosuppression. The mortality rate of SARS is higher than influenza and other respiratory tract illnesses. The overall mortality is more than 10% and is more than 50% in elderly individuals above 65 years.

Epidemiology

SARS is restricted in its geographical distribution.

 Geographical distribution

The SARS outbreak in 2002–2003 predominantly affected mainland China, Hong Kong, Singapore, Taiwan, and Canada. The SARS strain is believed to have originated in Guangdong province in southern China. The disease is epidemiologically linked to the National Institute of Virology in Beijing, where the outbreak is thought to have originated. A total of 8098 cases, 774 deaths, and 7324 recoveries from SARS were docu-mented between November 2002 and April 21, 2004.

 Reservoir, source, and transmission of infection

SARS is believed to be primarily transmitted by close person-to-person contact. Most cases of SARS were seen in indi-viduals who lived with or cared for a patient with SARS or who had exposure to contaminated secretions from a SARS patient.

The infection would possibly have been acquired by inhalation of infectious droplets during the act of coughing or sneezing, from a SARS patient. Moreover, another possible mode of transmission is direct contact of the eyes, nose, or mouth of susceptible individuals with infectious secretions of SARS patients.

Laboratory Diagnosis

Laboratory diagnostic tests are most essential to confirm diag-nosis of the SARS.

 Specimens

Specimens include respiratory secretions for isolation of virus, and serum for testing of antibodies.

 Isolation of the virus

SARS-CoV can be isolated in viral cultures. Isolation of virus is attempted only in class III laboratories.

 Serodiagnosis

Serodiagnosis of SARS depends on detection of specific anti-bodies to SARS-CoV in serum obtained during acute illness or 28 days and more after the onset of disease. IFA and ELISAs are the most frequently used tests for detection of specific antibodies in patients with SARS. Demonstration of a four-fold rise of antibody titer between acute and convalescent (.28 days after symptom onset) serum samples is suggestive of SARS.

Treatment

No specific antiviral treatment is available against SARS. Treatment is mostly symptomatic as given for a serious com-munity-acquired pneumonia.

Prevention and Control

Isolation of patient and strict barrier nursing is crucial to prevent transmission of SARS to others. Moreover, airport screening for potentially sick and/or febrile passengers is being carried out in SARS-affected regions in Asia by using infrared scanners. These scanners identify potentially febrile passen-gers by measuring their body heat. The software in the scan-ner is color-coded in temperature ranges; as skin temperature increases, the colors on the scanner change, such as black to green to yellow and, finally, to red. Any individual with a skin temperature of 37.5°C or greater glows bright red on the scan-ner. This, however, shows a lot of false-positive reactions, as many other noninfectious conditions (sunburn, ingestion of alcoholic beverages, recent cigarette smoking, or brisk exercise, etc.) can cause an increase in the skin temperature.


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