Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Interferons

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Other complications of influenza include infections of

the heart and heart lining, infections of the brain, and Guillain-

Barre syndrome (GBS). GBS is a paralytic disease in which

the body slowly becomes paralyzed. Paralysis starts in the

facial muscles and moves downward. GBS is treated sympto-

matically and usually resolves by itself. Another complication

of influenza is Reye’s syndrome. Occurring typically in chil-

dren, Reye’s syndrome is associated with aspirin intake during

an attack of influenza. Reye’s syndrome is characterized by

nausea, vomiting, and progressive neurological dysfunction.

Because of the risk of Reye’s syndrome, children should not

be given aspirin if they have the flu. Non-aspirin pain reliev-

ers, such as acetaminophen, should be given instead of aspirin.

Flu is treated with rest and fluids. Maintaining a high

fluid intake is important, because fluids increase the flow of

respiratory secretions, which may prevent pneumonia.

Antiviral medications (amantadine, rimantadine) may be pre-

scribed for people who have initial symptoms of the flu and

who are at high risk for complications. This medication does

not prevent the illness, but reduces its duration and severity.

A flu vaccine is available that is formulated each year

against the current type and strain of flu virus. The virus is

grown in chicken eggs, extracted, and then rendered noninfec-

tive by chemicals. The vaccine is also updated to the current

viral strain by the addition of proteins that match the current

strain’s composition. The vaccine would be most effective in

reducing attack rates if it was effective in preventing influenza

in schoolchildren; however, in vaccine trials the vaccine has

not been shown to be effective in flu prevention in this age

group. In certain populations, particularly the elderly, the vac-

cine is effective in preventing serious complications of

influenza and thus lowers mortality.

Vaccine research is ongoing. One of the more exciting

advances in flu vaccines involves research studies examining

an influenza vaccine mist, which is sprayed into the nose. This

is predicted to be an excellent route of administration, which

will confer even stronger immunity against influenza. Because

it uses a live virus, it encourages a strong immune response.

Furthermore, it is thought to be a more acceptable immuniza-

tionroute for schoolchildren, an important reservoir of the

influenza virus.

See alsoFlu: The great flu epidemic of 1918; Viruses and

responses to viral infection

INSTITUTE FORGENOMICRESEARCH•

seeTHEINSTITUTE FORGENOMICRESEARCH(TIGR)

IInterferon actionsNTERFERON ACTIONS

Interferonsare species-specific proteins, which induce antivi-

ral and antiproliferative responses in animal cells. They are a

major defense against viral infections and abnormal growths

(neoplasms). Interferons are produced in response to penetra-

tion of animal cells by viral (or synthetic) nucleic acid and

then leave the infected cell to confer resistance on other cells

of the organism. In contrast to antibodies, interferons are not

virus specific but host specific. Thus, viral infections of

human cells are inhibited only by human interferon. The

human genome contains 14 nonallelic and 9 allelic genes of α-

interferon (macrophage interferon), as well as a single gene

for β-interferon (fibroblast interferon). Genes for any two or

more variants of interferon, which have originated from the

same wild-type gene are called allelic genes and will occupy

the same chromosomal location (locus). Variants originating

from different standard genes are termed non allelic. α- and β-

interferons are structurally related glycoproteins of 166 and

169 amino acid residues. In contrast, γ-interferon (also known

as immune interferon) is not closely related to the other two

and is not induced by virus infection. It is produced by T-cells

after stimulation with the cytokine interleukin-2. It enhances

the cytotoxic activity of T-cells, macrophages and natural

killer cells and thus has antiproliferative effects. It also

increases the production of antibodies in response to antigens

administered simultaneously with α-interferon, possible by

enhancing the antigen-presenting function of macrophages.

Interferons bind to specific receptors on the cell surface,

and induce a signal in the cell interior. Two induction mecha-

nisms have been elucidated. One mechanism involves the

induction of protein kinase by interferon, which, in the pres-

ence of double-stranded RNA, phosphorylates one subunit of

an initiation factor of protein synthesis(eIF-2B), causing the

factor to be inactivated by sequestration in a complex. The

second mechanism involves the induction of the enzyme 2’,5’-

oligoadenylate synthetase (2’,5’-oligo A synthetase). In the

presence of double-stranded RNA, this enzyme catalyses the

polymerization of ATP into oligomers of 2 to 15 adenosine

monophosphate residues which are linked by phosphodiester

bonds between the position 2’ of one ribose and 5’ of the next.

These 2’,5’-oligoadenylates activate an interferon specific

RNAase, a latent endonuclease known as RNAase L which is

always present but not normally active. RNAase cleaves both

viral and cellular single stranded mRNA. Interferons therefore

do not directly protect cells against viral infection, but rather

render cells less suitable as an environment for viral replica-

tion. This condition is known as the antiviral state.

See alsoAntibody and antigen; Immune system; Immunology;

Viruses and responses to viral infection

IInterferonsNTERFERONS

Interferon is the name given to a group of proteins known pri-

marily for their role in inhibiting viral infections and in stim-

ulating the entire immune systemto fight disease. Research

has also shown that these proteins play numerous roles in reg-

ulating many kinds of cell functions. Interferons can promote

or hinder the ability of some cells to differentiate, that is, to

become specialized in their function. They can inhibit cell

division, which is one reason why they hold promise for stop-

ping cancer growth. Recent studies have also found that one

interferon may play an important role in the early biological

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