Question

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3. Answer the following questions that are based on the information in the abstract shown below. Jin H, Zhou H, Liu H, Chan W, Adhikary L, Mahmood K, Lee MS, Kemble G. (2005)Two residues in the hemagglutinin of A/Fujian 411/02-like influenza viruses are responsible for antigenic drift from A/Panama/2007/99. Virology 336(1):113-9. The H3N2 vaccine strain (A/Panama/2007/99) for the 2003-2004 influenza season did not antigenically match the circulating A/Fujian/411/02-like H3N2 viruses and had reduced effectiveness against influenza outbreaks. A/Wyoming/03/2003, an A/Fujian-like virus, was recommended as the vaccine strain for the 2004-2005 season. A/Wyoming differed from A/Panama by 16 amino acids in the HA1 molecule. Reverse genetics was used to determine the minimal amino acid changes that were responsible for the antigenic drift from A/Panama to A/Wyoming. After substitutions of 2 of the 16 amino acids in the HA (H155T, 0156H), the A/Panama HA variant was antigenically equivalent to A/Wyoming as determined by hemagglutination inhibition and microneutralization assays using ferret postinfection antisera. Conversely, AWyoming containing the His-155 and Gin-156 residues from AVPanama was antigenically equivalent to A/Panama. These results indicated that only these two HA residues specified the antigenic drift from A/Panama to A/Wyoming; other amino acid differences between these two H3N2 viruses had minimal impact on virus antigenicity but impacted virus replication efficiency in eggs. When discussing viral biology, what is a reservoir? . What is the reservoir for the avian influenza A virus? . What is the serotype of the A/Panama virus being discussed in this abstract? What is the genetic mechanism responsible for antigenic drift? . . Did the antigenic drift that created the A/Wyoming virus change the serotype? . When you examine the kinds of mutations that occur in the influenza virus over time, why do silent (synonymous) amino acid changes accumulate more rapidly than replacement (non-synonymous) amino acid changes? . The researchers report that of the 16 replacement changes that occurred in the A/Wyoming virus only 2 were responsible for making the vaccine ineffective. In what region of the Hemagglutinin protein did these amino acids likely reside? Explain your answer

Answer 1

1. When discussing viral biology, what is a reservoir?

Any person, animal, plant, soil or substance in which an infectious agent normally lives and multiplies are called Reservoir of infection. The reservoir typically harbors the infectious agent without injury to itself and serves as a source from which other individuals can be infected.

2. What is the reservoir for the avian influenza virus?

Airborne transmission of avian influenza virus from farm to farm is not likely. H5N1 HPAI can be spread from birds to people because of direct contact with infected birds, such as during home slaughter and plucking of infected poultry.

3. What is the serotype of the A/Panama virus being discussed in the abstract?

A/Fujian/411/02

4. What is the genetic mechanism responsible for antigenic drift?

Reverse genetics

5. Did the antigenic drift that created the A/ Wyoming virus change the serotype?

Yes. A change of as few as two amino acids (H155T and Q156H) could result in significant antigenic drift from A/Panama to A/Wyoming. The residues 155 and 156 are located in the tip of the HA structure and are easily accessible to antibodies. Since 1968, when the first influenza H3N2 strain emerged in humans, residues 155 and 156 have gone through significant evolution, from the original TK of A/HK/68 to YK, YE, HE, HK, HQ, and TH in the HA of the current A/Fujian/411/02-like strains. The frequent changes of these two residues most likely correlated with the antigenic drift of these H3N2 viruses in the past. Replacing the 155 and 156 residues of A/Panama HA with those of A/Wyoming restricted virus replication in eggs. However, A/Wyoming that contained the 155 and 156 residues from A/Panama grew efficiently in eggs. These data indicated that mutations in the HA tip region at these two residues affected virus replication differently.

6. When you examine the kinds of mutation that occur in the influenza virus over time. Why do silent (synonymous) aminoacid changes accumulate more rapidly than replacement (non-synonumous) aminoacid changes?

synonymous sub-stitutions is any changes at the nucleotide level that do not vary the amino acid sequence. Conversely, changes in the second position of the glycine codon can cause changes in the resulting amino acid sequence (for example, GCG codify for alanine) and represent a non-synonymous substitution

Lets for example

                          18 out of 20 amino acids are encoded by more than one codon

For instance, GGG, GGA, GGU, GGC codify all for glycine

Every change in the third position of a codon for glycine leads to a codon that ribosomes interpret equivalently for the construction of the primary structure of the protein

Therefore, silent (synonymous) aminoacid changes accumulate more rapidly than replacement (non-synonumous) aminoacid changes.

The researcher report that of the 16 replacement changes that occurred in the A/Wyoming virus only 2 were responsible for making the vaccine ineffective. In what region of hemagglutinin protein did these aminoacid likely reside? Explain your answer.

A/Panama and A/Fujian differed from each other by 13 amino acids in the HA1 region (Table 1). A/Wyoming, which is antigenically similar to A/Fujian, had three additional amino acid changes in the HA1 compared to that of A/Fujian. These three HA residues in A/Wyoming enabled efficient virus replication in embryonated chicken eggs. Ten of the 16 amino acid differences between A/Panama and A/Wyoming are located in the distal head of the HA trimer in close proximity of the HA receptor binding sites or the five main antigenic regions. The two amino acid changes at positions 155 and 156 in the HA1 altered the antigenicity of influenza A H3N2 viruses