Ortomyxoviruses. Influenza Virus.

Question 1

Classification

Answer 1

Family: orthomyxoviridae

Genus: influenzavirus

Species:

Influenza A virus
Influenza B virus
Influenza C virus

Question 2

Characteristics

Answer 2

• enveloped virus
• helical nucleocapsid
• -ssRNA
• RNA polymerase in virion
• replication in nucleus
• 8 viral segments
• two major antigens:
  > Hemagglutinin (HA)

> Neuraminidase (NA)

They determine the serotype —> type A, B, C influenza

Segments : important information due to mutations
Two broad categories of mutation:
> antigenic drift
——point mutation in the viral genome leading to changes in HA or NA
—— cause epidemics (disease outbreak limited to one geographical area)
Example: seasonal flu

> antigenic shift
—— more severe
—— antigenic segments of RNA are shared between different species
—— responsible for pandemics (occur over multiple continents or worldwide)

Question 3

Transmission

Answer 3

• respiratory droplets —> mainly between December to February

WINTER!

Question 4

Pathogenesis

Answer 4

Infection is limited to the epithelium of the respiratory tract

1) HA binds to sialic acid of cell membranes (URTs or RBCs)
2) Virus is endocytosed into the cell
3) M2 protein (a proton channel) makes pH optimal for viral encoding
4) Viral replication occurs in the nucleus of the host cell
5) NA cleaves sialic acid to allow release of new virions from the host cell

HA cause RBCs to agglutinate

Question 5

Disease

Answer 5

Influenza
- influenza A virus:
Most important out of the three
The cause of epidemics and pandemics outbreaks

• influenza B virus:
  Cause endemic outbreaks

A pandemic caused by swine origin strain H1N1 influenza A virus began in 2009

> major complication = pneumonia (coinfection with S.aureus or S.pneumoniae typically)

• associated with [Guillain-Barre Syndrome] of Campylobacter jejuni
  ~ ascending paralysis —> albuminocytologic dissociation (in CSF) = increased protein content with decreased WBC count

Giving aspirin to children due to wrong diagnosis/ auto-medication —> Reye’s syndrome = encephalitis + liver failure (fatty liver)

—> extensive damage to mitochondria. Associated with:

• fever
• rash
• jaundice

Question 6

Microbiological diagnosis

Answer 6

• Rapid ELISA test to detect influenza viral antigen in respiratory secretions
• it is identified by hemagglutination inhibition or complement fixation
• a four-fold or great antibody titer rise in convalescent-phase serum is diagnostic

Question 7

Treatment and prevention

Answer 7

Treatment:

Neuraminidase inhibitor: oseltamivir/ Anamivir (Tamiflu) is the drug of choice —> inhibit virion release

Amantadine and Rimantadine are no longer used due to widespread resistance
- they inhibit M2 protein —> do not allow viral replication

Prevention:

1) A killed vaccine containing purified HA and NA —> IV
2) live-attenuated Intranasal vaccine —> temperature sensitive mutant of influenza virus

Children can receive from the age of 6 months

Typically given in October

Oseltamivir (Tamiflu) can be used for prophylaxis in unimmunized people who have been exposed.