Page 325 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART IV Clinical Virology
314
Chicken
Human
influenza
influenza
inhibit the production of interferon mRNA. As a result,
virus
virus
innate defenses are reduced and viral virulence is corre-
spondingly enhanced.
Many species of animals (e.g., aquatic birds, chickens,
swine, and horses) have their own influenza A viruses.
These animal viruses are the source of the RNA segments
that encode the antigenic shift variants that cause epidem-
ics among humans. For example, if an avian and a human
influenza A virus infect the same cell (e.g., in a farmer’s
mebooksfree.com mebooksfree.com RNA genome segments agglutinin, may appear (see Figure 39–1). mebooksfree.com mebooksfree.com
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respiratory tract), reassortment could occur and a new
Lung cell
variant of the human A virus, bearing the avian virus hem-
There is evidence that aquatic birds (waterfowl) are a
Reassortment of
common source of these new genes and that the reassort-
ment event leading to new human strains occurs in pigs. In
other words, pigs may serve as the “mixing bowl” within
which the human, avian, and swine viruses reassort. There
are 16 types of hemagglutinin (H1 to H16) and 9 types of
neuraminidase (N1 to N9) found in waterfowl. In humans,
three types of hemagglutinin (H1, H2, and H3) and two
types of neuraminidase (N1 and N2) predominate.
New strain
Because influenza B virus is only a human virus, there is
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of influenza
no animal source of new RNA segments. Influenza B virus
virus
therefore does not undergo antigenic shifts. It does, how-
FIGURE 39–2
Antigenic shift in influenza virus. A human
strain of influenza virus containing the gene encoding one antigenic
must be included in the new version of the influenza vac-
type of hemagglutinin (colored orange) infects the same lung cell as
cine produced each year. Influenza B virus has no antigens
a chicken strain of influenza virus containing the gene encoding a
in common with influenza A virus.
different antigenic type of hemagglutinin (colored black). Reassort-
A/Philippines/82 (H3N2) illustrates the nomenclature
ment of the genome RNA segments that encode the hemagglutinin
of influenza viruses. “A” refers to the group antigen. Next
occurs, and a new strain of influenza virus is produced containing the
are the location and year the virus was isolated. H3N2 is the
chicken type of hemagglutinin (colored black).
(N) types. The H1N1 and H3N2 strains of influenza A
virion after it enters the cell. It transports protons into the
virus are the most common at this time and are the strains
virion causing the disruption of the envelope, which frees designation of the hemagglutinin (H) and neuraminidase
included in the current vaccine. The H2N2 strain caused a
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the nucleocapsid containing the genome RNA, allowing it
pandemic in 1957.
to migrate to the nucleus.
Summary of Replicative Cycle
Influenza viruses have both group-specific and type-
specific antigens.
interacts with sialic acid receptors on the cell surface. (The
(1) The internal ribonucleoprotein in the nucleocapsid
hemagglutinin on the virion surface is cleaved by extracel-
is the group-specific antigen that distinguishes influenza A,
lular proteases to generate a modified hemagglutinin that
B, and C viruses.
actually mediates attachment to the cell surface.) The virus
(2) The hemagglutinin and the neuraminidase are the
then enters the cell in vesicles and uncoats within an endo-
type-specific antigens located on the surface. Antibody
some. Uncoating is facilitated by the low pH within the
against the hemagglutinin neutralizes the infectivity of the
endosome. Protons pass through the ion channel formed
virus (and prevents disease), whereas antibody against the
by the M2 protein into the interior of the virion. This dis-
group-specific antigen (which is located internally) does
rupts the virion envelope and frees the nucleocapsid to
not. Antibody against the neuraminidase does not neutral-
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ize infectivity but does reduce disease by decreasing the
the genome RNA is transcribed.
amount of virus released from the infected cell and thus
The virion RNA polymerase transcribes the eight
reducing spread of the virus to adjacent cells.
genome segments into eight mRNAs in the nucleus. Syn-
thesis of the eight mRNAs occurs in the nucleus because a
An important determinant of the virulence of this virus
methylated guanosine “cap” is required. The cap is obtained
is a nonstructural protein called NS-1 encoded by the
from cellular nuclear RNAs in a process called “cap
genome RNA of influenza virus. NS-1 has several
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