Influenza

Question 1

Most common symptoms of uncomplicated influenza

Answer 1

Fever, cough, malaise. Self-limited.

Question 2

How to distinguish influenza from the common cold (rhino, adeno, corona)?

Answer 2

Systemic symptoms like fever + chills, headaches and myalgias, anorexia and malaise. Abrupt onset with duration ~ 3 days.

Question 3

What other symptoms, aside from systemic symptoms, are caused by influenza?

Answer 3

Respiratory symptoms= dry cough, sore throat, rhinorrhea, sneezing is more frequent with adeno/corona/rhinoviruses than the flu. Duration ~7-8 days, usually persist/worsen after resolution of systemic symptoms.

Question 4

Complications of influenza

Answer 4

Primary viral pneumonia, secondary bacterial pneumonia, myositis, myoglobinuria, myocarditis, toxic shock syndrome, guillain barre syndrome.

Question 5

Primary viral pneumonia

Answer 5

Extension of the URI into the LRT, begins like uncomplicated influenza, but gets progressively worse, can cause diffuse bilateral/multilobar opacities.

Question 6

Secondary bacterial pneumonia

Answer 6

Follows seemingly uncomplicated flu, biphasic illness = initial improvement, but 4-14 days later, bacterial pneumonia sets in. Focal consolidation. Generally caused by strep pneumo or s aureus, rather than h. influenzae.

Question 7

Influenza family

Answer 7

Orthomyxoviridae, groups ABC

Question 8

Structure of the flu virus

Answer 8

Negative-sense (genome is complementary to mRNA, segmented (7 or 8 RNAs per genome), nucleoprotein, which binds genomic viral RNA

Question 9

NP + vRNA

Answer 9

Ribonucleoprotein complex, a stable complex that remains similar across many virus strains, the target of most diagnostic tests.

Question 10

How to make clinical diagnosis:

Answer 10

flu season + fever + cough = flu

Question 11

RIDT

Answer 11

Rapid influenza diagnostic testing, an enzyme immunoassay that looks for NP. Very specific (98%), only 62% sensitive (some false negatives).

Question 12

DFA test for flu

Answer 12

Direct fluorescent antigen, best test. Epithelial cells from nasopharynx put on slide, stained with fluorescently labeled flu specific antibodies.

Question 13

Neuraminidase

Answer 13

NA for short, receptor destroying glycoprotein that is expressed on the viral surface, enhances the efficiency of progeny virus release from infected cells, target of protective antibody responses (but less so than hemagluttinin)

Question 14

Osteltamivir and Zanamivir

Answer 14

two antivirals that target neuraminidase, allow sialic acid to be cleaved before galactose to cause efficient egress of progeny virus.

Question 15

M2

Answer 15

Matrix 2, ion channel in the viral envelope, proton flux acidifies endosomes for fusion and uncoating, target of a non-neutralizing antibody response

Question 16

Amantadine and Rimantadine

Answer 16

Two antivirals that target M2. Orally administrated, inhibits pH-dependent virus endosome fusion and genome uncoating. Active only against influenza A. Side effects = CNS, N/V, loss of appetite.

Question 17

Influenza life cycle

Answer 17

Attachment with HA binding to sialic acid, entry via endocytosis, fusion with endosome and uncoating (this step is blocked by amantidine and rimantidine), viral genome is imported into the nucleus where mRNA is synthesized, exported, translated and modified, packaged and exported. To enable release, NA must destroy sialic acid to let the virus go. Osteltamivir and zanamivir block this step, preventing release.

Question 18

Oseltamivir

Answer 18

Oral, standard adult dose 75mg 2x/day x 5 days. Prodrug that is cleaved by hepatic esterases to create a carboxylate. Renally cleared, can cause N/V.

Question 19

Zanamivir

Answer 19

Inhaled 10mg 2x/day for direct delivery to respiratory tract. Contraindicated in reactive airway disease (asthma/COPD) due to bronchospasm.

Question 20

Adamantane resistance

Answer 20

Very easy, a single point mutation in the M2 ion channel is sufficient to confer resistance. This mutation doesn’t affect viral function, just antiviral function. All influenza A viruses circulating currently have adamantane resistance.

Question 21

Target of the majority of the neutralizing antibody response?

Answer 21

Hemagglutinin, receptior binding glycoprotein expressed on the viral surface.

Question 22

Antigenic drift

Answer 22

Over time, accumulating amino acid mutations in HA eventually enable escape from antibody recognition. Enables reinfection of previously infected hosts.

Question 23

Antigenic shift

Answer 23

Novel HA genes from the animal reservoir can result in a virus to which the human population in immunologically naive.

Question 24

Polymerase complex (PA, PB1 and PB2)

Answer 24

RNA-dependent RNA polymerase, transcribes (-)sense genomic viral RNA into + sense mRNA for translation of viral proteins by host cell machinery, AND complementary RNA. No proofreading, so very error prone, 1 misincorporation per 10^3-10^5 nts. These mutations can be advantageous! For example, mutation in HA helps evade antibodies (antigenic drift), mutation in M2 to NA confers drug resistance.

Question 25

Influenza vaccine primary immunogen

Answer 25

HA! Body creates anti-HA antibodies to neutralize (prevent infection by preseting receptor binding) or non-neutralize (preventing endosome fusion).

Question 26

Trivalence

Answer 26

Prevents against 2 types of influenza A (H1N1, H3N2) and B.

Question 27

Split Virus Vaccine

Answer 27

Egg-grown viruses are distrupted with a detergine to solubilize the viral membrane, releasing surface glycoproteins HA and NA.

Question 28

Subunit Vaccine

Answer 28

After detergent treatment, the surface proteins are separated out from the rest of the virus components.

Question 29

Attenuated Vaccine

Answer 29

Backbone is an influenza virus that grows poorly above 35 degrees C.

Question 30

Recombinated HA influenza vaccine

Answer 30

(RIV), antigens are grown in culture (HA), rapid production, shorter shelf life, similar immunogenicity and efficacy.