Orthomyxoviruses

Retno BudiartiMicrobiology department

FK UHT

Properties Virion: Spherical, helical nucleocapsid divided into 3 types: influenza A, B, and C.

The current subtypes of influenza A viruses found in people are H1N1 and H3N2.

Genome: Single-stranded RNA, segmented (eight molecules), negative-sense 

Proteins: 9 structural proteins, one nonstructural 

Envelope: Contains viral hemagglutinin (HA) and neuraminidase (NA) proteins 

structure A lipid envelope derived from the cell

surrounds the virus particle. Glycoprotein :Hemagglutinin (HA) and the

neuraminidase (NA), are inserted into the envelope and are exposed as spikes about 10 nm long on the surface of the particle.

These glycoproteins are the important Ag that determine antigenic variation and host immunity.

structure

Because of the segmented nature of the genome, when a cell is coinfected by two different viruses of a given type, mixtures of parental gene segments may be assembled into progeny virions.

This phenomenon, called genetic reassortment, may result in sudden changes in viral surface antigens

Hemagglutinin 15 subtypes of HA (H1–H15) binds virus particles to susceptible cells is the major antigen ability to agglutinate erythrocytes The cleavage that separates into HA1 and HA2

is necessary for the virus particle to be infectious and is mediated by cellular proteases. Enzymes that cleave HA are common only at respiratory tract

The amino terminal of HA2, generated by the cleavage event, is necessary for the viral envelope to fuse with the cell membrane, an essential step in the process of viral infection

Neuraminidase important in determining the subtype of virus The spike on the virus particle is a tetramer,

composed of four identical monomers. There is a catalytic site for NA on the top of each head, so that each NA spike contains four active sites

The NA functions at the end of the viral replication cycle. It is a sialidase enzyme. It facilitates release of virus particles from infected cell surfaces during the budding process and helps prevent self-aggregation of virions by removing sialic acid residues from viral glycoproteins.

Helps the virus through the mucin layer in the resp tract to reach the target epithelial cells.

Antigenic Drift Minor antigenic changes the accumulation of point mutations in

the gene, resulting in amino acid changes in the protein

Sequence changes can alter antigenic sites on the molecule such that a virion can escape recognition by the host's immune system

A variant must sustain two or more mutations before a new, epidemiologically significant strain emerges

Antigenic Shift major antigenic changes in HA or NA drastic changes in the sequence of a

viral surface protein The segmented genomes of influenza

viruses reassort readily in doubly infected cells

The mechanism for shift is genetic reassortment between human and avian influenza viruses

Influenza Virus Replication

Pathogenesis & Pathology by airborne droplets or by contact with

contaminated hands or surfaces A few cells of respiratory epithelium are

infected if deposited virus particles avoid removal by the cough reflex and escape neutralization by preexisting specific IgA antibodies or inactivation by nonspecific inhibitors in the mucous secretions

Within a short time, many cells in the respiratory tract are infected

Pathogenesis & Pathology

Cell death at later times may also result from the actions of cytotoxic T-cells. As a result, the efficiency of ciliary clearance is reduced, leading to impaired function of the mucus elevator; thus there is reduced clearance of infectious agents from the respiratory tract.

Pathogenesis & Pathology The incubation period :1 to 4 days Viral shedding starts the day preceding onset

of symptoms, peaks within 24 hours, remains elevated for 1–2 days, and then declines over the next 5 days

cellular destruction and desquamation of superficial mucosa of the respiratory tract but do not affect the basal layer of epithelium

Viral damage to the respiratory tract epithelium lowers its resistance to secondary bacterial invaders, especially staphylococci, streptococci, and Haemophilus influenzae.

Clinical Findings

Uncomplicated Influenza : Fever (38 - 40 degrees C), Myalgias, headache, Ocular symptoms - photophobia, tears, ache, Dry cough, nasal discharge, H1N1 strain, the 2009 "swine flu", also gives rise to gastro-intestinal symptoms (e.g. vomiting, diarrhea)

Pneumonia

Immunity long-lived and subtype-specific Antibodies against HA and NA are

important in immunity to influenza Immunity can be incomplete, as

reinfection with the same virus can occur

The three types of influenza viruses are antigenically unrelated and therefore induce no cross-protection

Laboratory Diagnosis Isolation and Identification of Virus :

embryonated eggs, Cell cultures can be tested for the presence of virus by hemadsorption 3–5 days after inoculation

Serology : Antibodies to several viral proteins (hemagglutinin, neuraminidase, nucleoprotein, and matrix)

Avian Influenza Of the 16 HA subtypes found in birds, only

a few have been transferred to mammals (H1, H2, H3, and H5 in humans; H1 and H3 in swine; and H3 and H7 in horses).

nine NA subtypes are known for birds, only two of which are found in humans (N1, N2).

The influenza viruses do not appear to undergo antigenic change in the birds, perhaps because of their brief life span.

Avian Influenza..

human pandemic strains have been reassortants between avian and human influenza viruses. Pigs serve as mixing vessels for reassortants as their cells contain receptors recognized by both human and avian viruses

Avian Influenza.. In 1997, in Hong Kong, the first

documented infection of humans by avian influenza A virus (H5N1) occurred. The source was domestic poultry.

In 2006, the presence of this highly pathogenic H5N1 avian influenza virus in both wild and domestic birds had expanded to include many countries.

Isolates from human cases have contained all RNA gene segments from avian viruses, the avian virus had jumped directly from bird to human.

treatment

Amantadine hydrochloride, rimantadine, are M2 ion channel inhibitors for systemic use in the treatment and prophylaxis of influenza A.

The NA inhibitors zanamivir and oseltamivir for treatment of both influenza A and influenza B

vaccines Inactivated viral vaccines are the

primary means of prevention of influenza

licensed for parenteral use in humans The vaccine is usually a cocktail

containing one or two type A viruses and a type B virus of the strains isolated in the previous winter's outbreaks.

vaccines

Selected viruses strains are grown in embryonated eggs.

The reassortant virus, which carries the genes for the surface antigens of the desired vaccine with the replication genes from an egg-adapted laboratory virus, is then used for vaccine production

vaccines Vaccines are either whole virus (WV),

subvirion (SV), or surface antigen preparations.

The WV vaccine contains intact, inactivated virus; the SV vaccine contains purified virus disrupted with detergents; and the surface antigen vaccines contain purified HA and NA glycoproteins. All are efficacious.

live attenuated, cold-adapted, temperature-sensitive, trivalent influenza virus vaccine administered by nasal spray was licensed in the United States in 2003

Corona virus

enveloped an unsegmented genome of single-

stranded positive-sense RNA the largest positive strand RNA

viruses do not grow well in cell culture

Replication:- Inside the host cell, the capsid busts

open and releases viral components- single positive strand RNA has a double

role in the viral life cycle of SARS-CoV because not only it acts as a template for replication, but also as the first viral mRNA.

- by action of RNA polymerase, the positive ssRNA is being translated.

The RNA-dependent-RNA polymerase continues making viral mRNA that constantly being used to synthesize viral proteins.

Other viral genes are also being translated to produce: spike(S), envelope (E), membrane (M), and nucleocapsid (N) that binds to the RNA genome

As a result of this rapid process, can be used up within hours, causing the extensive damage and deterioration of the host cell. At the same time, SARS-CoV also replicate their entire genomic RNA in the cytoplasm of the host cell.

S protein can bind to sialic acid on the host cell surface which gives the virus a hemagglutinating ability.

HE protein can cleave the sialic acid from a sugar chain, which may aid the virus in escaping from the cell in which it was replicated

M protein helps in the attachment of the nucleocapsid to the membranes of internal structures such as the Golgi Body

Coronavirus Infections in Humans tropism for epithelial cells of the

respiratory or gastrointestinal tract the outbreak of SARS in 2003 was

characterized by serious respiratory illness, including pneumonia and progressive respiratory failure

the SARS virus originated in a nonhuman host and acquired the ability to infect humans

symptoms

malaise, chills, headache, dizziness, cough, and sore throat, followed a few days later by shortness of breath

The incubation period is 6 days Death from progressive respiratory

failure