Lecture 10: Virology -Orthomyxoviridae & paramyxoviridae

Question 1

Orthomyxoviridae & Paramyxoviridae

-similar how?

Answer 1

similar structures and the ability to adsorb to glycoprotein receptors particularly in the upper respiratory tract

Question 2

Orthomyxoviridae are all ______________ viruses, which case the “_____________”

Answer 2

influenza; ordinary flu

Question 3

Paramyxoviridae also replicate in the _________________ and can produce a parade of distinctly different diseases.

Answer 3

upper respiratory tract

Question 4

Paramyxoviridae include what viruses?

Answer 4

Parainfluenza virus, mumps, measles, and respiratory synctial virus

Question 5

Approximately 20% of world’s population gets infected with the ____________ virus each year

Answer 5

influenza

Question 6

In the US, influenza infection occurs as _________ influenza each winter, typically between late _______ and early _________ and up to __-___% of people get infected in certain communities

Answer 6

epidemic; December; March; 10-40%

Question 7

Symptoms of Influenza

-which symptoms set this apart from the run of the mill cold?

Answer 7

upper respiratory:
-dry cough
-sore throat
-rinorrhea (runny clogged nose)
painful muscle aches**
high fevers**
headaches**

Question 8

ORTHOMYXOVIRIDAE
Virion structure and Pathogenesis
   -what shape?
   -structure
   -what is on the outer membrane? what anchors them?
   -2 types of glycoprotein

Answer 8

• spherical virions
• Virion center has 8 segments of (-)RNA putt together with a protein (nucleocapsid protein) into a helical symmetry capsid
• surrounding the nucleocapsid lies an outer membrane studded with long glycoprotein spikes
• 2 distinct types of glycoprotein:
  1) Hemagglutin activity (HA)
  2) Neuraminidase activity (NA)
• Anchoring the bases of each of these spikes on the inside of the viral lipid bilayer are membrane proteins (M proteins)

Question 9

Hemagglutinin (HA)

• attaches where?
• causes what?
• needed for what?
• antibodies against HA do what?

Answer 9

• can attach to host sialic acid receptors present on the surface of erythrocyts
• viruses w/HA glycoproteins cause heme-agglutination when mixed with RBCs
• host cell sialic acid receptors also exist on upper respiratory tract cell membranes and HA binding to these receptors activates fusion of the host cell membrane with the virion membrane
• **HA is needed for adsorption
• antibodies against HA will block this binding and prevent infection

Question 10

Neuraminidase (NA)

• what is neuraminic acid?
• what does NA do?
• critical for what process? how?

Answer 10

• Neuraminic acid: important component of mucin and forms an integral part of the host’s upper respiratory defense barrier
• Neuraminidase (NA) cleaves neuraminic acid and disrupts the mucin barrier, exposing the sialic acid binding sites beneath
• critical for the release of the newly formed virion from the infected host cell
  
  • > as new viruses are assembled, they bud out of the host membrane and after budding is complete, the virion’s hemagglutinin is bound to a host cell sialic acid containing receptor
  • > NA then cleaves this sealic acid receptor to allow the formed virus to escape and infect a new cell

Question 11

Influenza Serology

Answer 11

• 3 types: A, B, and C
  
  • > these types have many strains separated by antigenic differences in HA and NA
• Type A infects humans, mammals (swine etc) and birds.
• Type B and C have only been isolated from humans

Question 12

Antigenic Drift

-(Influenza)

Answer 12

• during viral replications mutations can occur in the HA or NA, leading to changes in the antigenic nature of these glycoproteins
• changes are small
• resulting new strains are only partially attacked by our immune system, resulting in milder disease in adults who have previously acquired antibodies

Question 13

Antigenic Shift

-(Influenza)

Answer 13

• complete change of the HA, NA, or both
• *occurs only with influenza type A: involves the trading of RNA segments between animal and human strains
• when 2 influenza strains co-infect the same cell, undergo replication and capsid packaging, RNA segments can be mispackaged into another virus
• this virus now wields a new HA or NA glycoprotein that has never been exposed to the human immune system

Question 14

Influenza A subtype H1N1

-made up of what genetic elements? (x4)

Answer 14

• most common cause of influenza in humans
• 2009 flu pandemic, virus was found to be made up of genetic elements from 4 different flu viruses -N.American swine flu, N.American avian flu, human flu, and swine flu typically found in Asia and Europe
• Preliminary genetic characterization showed:
  a) HA gene -similar to swine flu viruses present in US pigs since 1999
  b) NA and matrix protein (M) genes -resembled versions present in European swine flu isolates

Question 15

Treatment of H1N1

Answer 15

Aniviral drugs:

1) Oseltamivir - NA inhibitor formulated as capsules or oral suspension, FDA approved for the treatment of uncomplicated acute influenza in patients 1 year and older who have been symptomatic for no more than 2 days
2) Zanamivir -NA inhibitor formulated for oral inhalation, FDA approved for the treatment of influenza patients 7 years and up who have uncomplicated illness and have been symptomatic for no more than 2 days
3) Paramivir - NA inhibitor formulated for intravenous (IV) administration, investigational product currently being evaluated in clinical trials

Question 16

PARAMYXOVIRIDAE
Structure and Pathogenesis
   -structure
   -genome
   -HA and NA differ from locations in ortho. how?
   -fusion protein
   -4 pathogens
   -Lungs, kids, viremia

Answer 16

-similar structure to orthomyxoviridae
- ss(-)RNA, not segmented
-HA and NA are part of the same glycoprotein spike, not 2 diff. spikes
-posses a fusion protein that causes the infected host cells to fuse together into multinucleated giant cells
-4 types that cause disease:
1) parainfluenza virus
2) respiratory syncytial virus (RSV)
3) mumps virus
4) measles virus
LUNGS-> all adsorb to and replicate in the upper respiratory tract. RSV and parainfluenza virus both cause lower respiratory infection (pneumonia) in children and upper respiratory infections (bad colds) in adults
KIDS-> most infections occur in children
VIREMIA (see next card)

Question 17

Paramyxoviridae

-Viremia

Answer 17

VIREMIA -> the viral infection results in dissemination of virions in the blood to different organs, mumps and measles reproduce in the upper respiratory tract and spread to distant organs
->mumps can produce local parotid and testes infection and measles can produce a severe systemic febrile illness. Brain infection (encephalitis) can occur with both mumps and measles

Question 18

Parainfluenza virus

Answer 18

• causes upper respiratory infection in adults ranging from cold symptoms such as rhinitis, pharyngitis, and sinus congestion to bronchitis and flu-like illness
• children, elderly, and immunocompromised also suffer from lower respiratory tract infections (pneumonia)

Question 19

Croup

Answer 19

a parainfluenza infection of the larynx and other upper respiratory structures (laryngotracheobronchitis) that occurs in children

Question 20

Respiratory Synctial Virus (RSV)

• causes what?
• contains what special protein?
• HA and NA differ how?
• # 1 cause of what?
• treatment vs. prevention

Answer 20

• causes respiratory infection and contains an F protein that causes formation of multinucleated giant cells (syncytial cells)
• lacks both HA and NA
• # 1 cause of pneumonia in young children esp. in infants less than 6 mo
• highly contagious with outbreaks in winter and spring
• Treatment w/ribavarin for severe disease condition has shown conflicting results
• Prevention with palivzumab, a monoclonal antibody against RSV is a better option

Question 21

Mumps Virus

• replicates where? spreads where?
• most frequently involved organs
• how many antigenic types?
• vaccine

Answer 21

• replicates in the upper respiratory tract and in regional lymph nodes and spreads via the blood to distant organs
• infection can occur in many organs but the most frequently involved is the parotid gland and also testes can be infected
• only one antigenic type, and a live attenuated viral vaccine is part of the trivalent measles-mumps-rubella (MMR) vaccine

Question 22

Measles Virus

• spread how?
• replicates where?
• how long is incubation period?

Answer 22

• highly contagious and spreads through nasopharyngeal secretions by air or direct contact
• multiplies in the respiratory mucous membranes and in the conjunctival membranes
• incubation lasts for 2 weeks prior to the development of rash

Question 23

Measles

-Prodrome

Answer 23

prior to the appearance of the rash the patient suffers from prodromal illness with conjunctivitis, swelling of the eyelids, photophobia, high fevers to 105F, hacking cough, rhinitis, and malaise

Question 24

Measles

-Koplik’s spots

Answer 24

a day or 2 before the rash, the patient develops small red-based lesions with blue white centers in the mouth

Question 25

Measles

-Rash

Answer 25

measles rash is red, flat to slightly bumpy (maculopapular)

-spreads out from the forehead to the face, neck, and torso and hits the feet by the third day