College of Medicine Microbiology



College of Medicine Microbiology

Medical Virology

RNA Viruses-related to respiratory tract: Dr.Jawad Kadhim

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Influenza virus:

• Genus: Influenzavirus.

Important properties:

• It is member of family orthomyxoviridae.

• Shape of virus is spherical.

• Symmetry of nucleocapsid is helical.

• Viral genome is segmented, and (-) ssRNA(7– 8 segments).

• Enveloped (bi-layer membrane).

• Spiked: 2 types antigens: H (Hemagglutinin for attachment of virus to target cell) and N( Neuraminidase for release of virus).

Classification :

• Influenza virus classified into three types according to group-specific antigens (nucleocapsid antigens): influenza A, B and C.

• Influenza type A and B contain 8 segments, while influenza type C has 7 segments of ssRNA.

• The influenza type A (only) can be divided into subtypes(serotypes) according to type-specific antigen( H and N antigens). So far, 16 subtypes of H (H1-H16) and 9 subtypes of N(N1-N9) were identified.

Source and transmission:

• Influenza A has broad host range capable of infecting human, swine, horses, chicken and birds(aquatic birds). Influenza B and C host range is limited to human only.

• Infected humans are main reservoir of infection. The virus transmitted from person to person by air-borne respiratory droplets and by contact with contaminated materials of patient.

• Avian influenza virus(influenza-A) cause bird flu in domestic poultry birds. Fortunately avian virus was poorly transmissible to human.

Antigenic variation:

• Because viral genome is segmented, genetic reassortment can occur during viral replication. The reassortment could lead to emergence of new human virus(new strain), the progeny of which will contain a mixture of genome segments from human and from animal strain. Therefore antigenic variation can occur due to mutation in sequence of amino acids in proteins of H and N. The mutation leads to change in antigenic nature of H or N or both resulting new strains that non-identified by immune system(escape from immune recognition).

Two types of variation are known:

• Antigenic shift( complete change in H or N or both). This can only occur with influenza type A because it has wide host range , when two different strains of viruses co-infect the same cell, during viral replication ,the RNA segments can be mis-packaged into another virus and release new strains. Antigenic shift is responsible for influenza pandemics.

• Antigenic drift(partial changes). This occurs in type A and B. It involves minor changes affecting H or N, not both. It is responsible for influenza epidemics.

• Antigenic variation of envelope proteins H and N is responsible for epidemic and pandemic diseases. Influenza A causes major epidemic disease (pandemic) with significant mortality. Influenza B causes sporadic and periodical epidemic disease, usually milder than influenza A. While the influenza C cause minor (mild), sub-clinical disease, because it stable antigenic and lack neuraminidase gene (the gene is located on segment which the type C hasn’t it).

N.B: Antigenic change not appears in birds, perhaps because of their brief life span.

Pathogenesis:

• Virus is limited to ciliated epithelial cells of respiratory tract.

• N antigen facilitates infection by reducing the viscosity of mucus lining by cleaves the substrate(neuramic acid) covering mucosal epithelial cells of respiratory tract and disrupts the mucin barrier ,then exposing the cell receptor for H antigen(H responsible for absorption). Then the virus enters by endocytosis into host cell.

• Within short time many cells in respiratory are infected and killed. The virus replicates within nucleus of infected cell and result in shut-off of host cell protein synthesis by 3 hr. and new progeny viruses are produced within 8-10 hr.s

• The virus remains localized to respiratory, hence viremia does not occur.

• The virus lead to death of epithelial cells . Denudation of respiratory epithelial cells causes acute inflammatory response and renders the individuals to bacterial super-infections.

• Antibodies provide long-lasting immunity (not long life immunity) against influenza infection.

C/F:

• I.P(1-4 days) dependent upon size of dose and immune status of human. Fever, headache, nose secretion, anorexia, cough, chills and generalized myalgia(muscle pain) are most clinical features. If no complication, the disease resolves in 2-7days.

• Complication of influenza ; individuals at greater risk for complication include elderly and immunocompromised people, the virus spreads to LRT , resulting in secondary infection such as bacterial pneumonia caused by Strep.pneumoniae ,Staph.aureus or Hemophilus influenzae .

Epidemiology:

• Influenza occurs primarily in winter months. In southern hemisphere, eg; in Australia, and New Zealand , influenza occurs in winter months of June through August.

• Most cases caused by Influenza type-A has been responsible for 3-5millions of infection worldwide.

• Influenza outbreak occurs in wave. Epidemic infection caused by type A occurs in each 2-3 years, while epidemic caused by type B is longer 3-6 years . Pandemic disease occurs every 10 years or more.

• Shift variants appear every 10 years, whereas drift variants appear every year (approximately).

• Standard nomenclature systems for influenza virus include; type, host, geographic, strain number, year of isolation and serotype. For example: A/swine/Iowa/15/30(H1N1).

• When bacterial pneumonia secondary to influenza cause a significant number of deaths especially in older people. Mortality rate may reach 40-60% in untreated cases.

• Global epidemic influenza infections:

1889. H2N2

1900. H3N2

1918. H1N1(Spanish flu due to swine flu that cause catastrophic pandemic, 20 million died with complicated bacterial pneumonia).

1957. H2N2(Asian flu)

1968. H3N2(Hong Kong flu)

1977. H1N1(Russian flu)

1997. H5N1

1999. H9N2 (bird flu)

2004. H5N1(bird flu)

2005. H5N1(bird flu)

2009 novel strain contains mixed genome (originated from bird as well as swine and human). New H1N1(in 2009).

Lab.Dx:

• Virus is isolated from clinical specimen(nasal washings, gargles, and throat swabs) in cell culture.

• Detection of specific antibodies level over 2 weeks by serological tests : CFT and ELISA

• Detection of viral nucleic acid by PCR.

• Detection of viral proteins.

Control methods:

a. Treatment:

• Amantadine and Rimantadine are used to prevent uncoating of influenza A. Whereas Sanamavir and Oseltamivir are inhibitors for neuraminidase in influenza A and B.

• Children given aspirin when they have influenza can develop a severe liver and brain disease called (Reyeʼs syndrome, it is severe encephalitis). Give acetaminophen for fever in children, no aspirin.

b. Prevention:

• Killed influenza A and B vaccine is given intramuscularly for elderly and immunocompromised patients. Attenuated influenza A vaccine (given spraying into nose ) is available for healthy adults and children. Because the virus undergo antigenic shift , the vaccine will not be effect in protecting against the new subtypes of virus . Therefore, it becomes necessary to develop a new vaccine as quickly as possible. Influenza vaccines give protection for 6 months.

• Personal hygiene and avoid contact with patients .

• Covering mouth and nose during coughing and sneezing with mask.

• Avian virus was controlled by destroying poultry.

Parainfluenza virus:

Genus : Respirovirus (parainfluenza type-1 and 3).

Genus : Rubulavirus( parainfluenza type-2,4a and 4b).

Important properties:

• It belongs to paramyxoviruses.

• ss(-)RNA, non-segmented.

• Helical nucleocapsid.

• Enveloped virus.

• Spiked(three glycoprotein: F, N, H).

Source and transmission:

• Humans are main sources.

• It transmitted by direct contact or aerosol.

Pathogenesis:

• Primary infection of URT , may involve nose, throat, resulting in common cold. The infection may move extensive and, especially with type-1,2 may involve larynx and upper trachea, resulting in croup (laryngotracheobranchitis). It is characterized by respiratory obstruction due to swelling of larynx and related structures.

• The infection may spread deeper to lower trachea and bronchi, resulting pneumonia or bronchiolitis, especially with type-3 (type-4 does not cause serious disease).

C/F:

• The I.P appears to be 5-6 days. The infection result in rhinitis and pharyngitis and pneumonia characterized with fever, headache, and cough.

• The most common complication of infection is otitis media.

Epidemiology:

• Parainfluenza viruses are widely distributed geographically.

• They are major cause of lower respiratory tract infection in young children.

• Type-3 is endemic, with some increase during spring, whereas type-1 and 2 tend to cause epidemics during fall or winter.

Dx.

• Isolation of virus in tissue culture.

• Serology by Nt, HI, or ELISA tests.

• Nucleic acid detection by PCR.

Control:

• Treatment with Ribavirin.

• No vaccine is available.

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