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 mebooksfree.com  mebooksfree.com           mebooksfree.com              pharynx, and lower respiratory tract sites such as the lar-  315  mebooksfree.com
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                                                                                      CHAPTER 39  RNA Enveloped Viruses
                        snatching.” Most of the mRNAs move to the cytoplasm,
                        where they are translated into viral proteins. Some of the
                                                                         ynx, trachea, and bronchi. Pneumonia, which involves the
                        viral mRNAs remain in the nucleus, where they serve as the
                                                                         alveoli may also occur.
                                                                           After the virus has been inhaled, the neuraminidase
                        template for the synthesis of the negative-strand RNA
                                                                         degrades the protective mucus layer, allowing the virus to
                        genomes for the progeny virions. Replication of the prog-
                        eny genomes is performed by a different subunit of the viral
                                                                         tract. The infection is limited primarily to this area because
                        RNA polymerase (acting as a replicase) from the subunit
                                                                         the proteases that cleave the hemagglutinin are located in
                        that functioned earlier as a transcriptase that synthesized
                                                                         the respiratory tract.
                        the mRNAs. Two newly synthesized proteins, NP protein   gain access to the cells of the upper and lower respiratory
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                        and matrix protein, bind to the progeny RNA genome in
                                                                           Despite systemic symptoms, viremia rarely occurs. The
 mebooksfree.com  mebooksfree.com           mebooksfree.com              superficial layers of the respiratory epithelium. Influenza       mebooksfree.com
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                                                                         systemic symptoms, such as severe myalgias, are due to
                        the nucleus, and that complex is transported to the
                                                                         cytokines circulating in the blood. There is necrosis of the
                        cytoplasm.
                          The helical ribonucleoprotein assembles in the cyto-
                        plasm, matrix protein mediates the interaction of the
                                                                         virus pneumonia, which can complicate influenza, is inter-
                        nucleocapsid with the envelope, and the virion is released
                                                                         stitial in location.
                        from the cell by budding from the outer cell membrane at
                                                                           Immunity depends mainly on secretory IgA in the respi-
                        the site where the hemagglutinin and neuraminidase are
                                                                         ratory tract. IgG is also produced but is less protective.
                                                                         Cytotoxic T cells also play a protective role.
                        located. The neuraminidase releases the virus by cleaving
                        neuraminic acid on the cell surface at the site of the bud-
                        ding progeny virions. Influenza virus, hepatitis delta virus,
                        and retroviruses are the  only RNA viruses that have an
                                                                         After an incubation period of 24 to 48 hours, fever, myal-
                        important stage of their replication take place in the   Clinical Findings
                                                                         gias, headache, sore throat, and cough develop suddenly.
                        nucleus.
                                                                                                            mebooksfree.com
 mebooksfree.com  mebooksfree.com           mebooksfree.com              in 4 to 7 days, but influenzal or bacterial pneumonia may         mebooksfree.com
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                                                                         Severe  myalgias (muscle pains) coupled with respiratory
                                                                         tract symptoms are typical of influenza. Vomiting and diar-
                        Transmission & Epidemiology
                                                                         rhea are rare. The symptoms usually resolve spontaneously
                        The virus is transmitted by airborne respiratory droplets.
                        The ability of influenza A virus to cause epidemics is
                                                                         complicate the course. One of the well-known complications
                        dependent on antigenic changes in the hemagglutinin and
                                                                         of influenza is pneumonia caused by either Staphylococcus
                        neuraminidase. As mentioned previously, influenza A virus
                                                                         aureus or Streptococcus pneumoniae.
                        undergoes both major antigenic shifts as well as minor
                                                                           Reye’s syndrome, characterized by encephalopathy and
                                                                         liver degeneration, is a rare, life-threatening complication
                        antigenic drifts. Antigenic shift variants appear infre-
                        quently, whereas drift variants appear virtually every year.
                        The last major antigenic shift that caused a pandemic in
                                                                         influenza B and chickenpox. Aspirin given to reduce fever
                        humans was in 1968 when H3N2 emerged. Epidemics and
                                                                         in viral infections has been implicated in the pathogenesis
                                                                         of Reye’s syndrome.
                        pandemics (worldwide epidemics) occur when the antige-  in children following some viral infections, particularly
                        nicity of the virus has changed sufficiently that the preexist-
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 mebooksfree.com  mebooksfree.com           mebooksfree.com              grounds, laboratory tests are available. The test most com-       mebooksfree.com
                        ing immunity of many people is no longer effective. The
                                                                         Laboratory Diagnosis
                        antigenicity of influenza B virus undergoes antigenic drift
                                                                         Although most diagnoses of influenza are made on clinical
                        but not antigenic shift. The antigenic changes exhibited by
                        influenza B virus are less dramatic and less frequent than
                                                                         monly used is an enzyme-linked immunosorbent assay
                        those of influenza A virus.
                                                                         (ELISA) for viral antigen in respiratory secretions such as
                          Influenza occurs primarily in the winter months of
                                                                         nasal or throat washings, nasal or throat swabs, or sputum.
                        December to February in the northern hemisphere, when
                                                                         Several rapid ELISA tests suitable for a physician’s office
                        influenza and bacterial pneumonia secondary to influenza
                                                                         laboratory are available. Two tests (FLU OIA and QuickVue
                        cause a significant number of deaths, especially in older
                                                                         Influenza Test) are based on detection of viral antigen using
                        people. The morbidity of influenza in children younger
                                                                         monoclonal antibodies, and a third test (ZSTATFLU) is
                        than 2 years is also very high, second only to the morbidity
                                                                         based on detection of viral neuraminidase using a substrate
                        in the elderly. In the southern hemisphere (e.g., in Australia
                                                                         of the enzyme that changes color when cleaved by neur-
                        and New Zealand), influenza occurs primarily in the winter
 mebooksfree.com  mebooksfree.com           mebooksfree.com              aminidase. The rationale for using the rapid tests is that        mebooksfree.com
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                        months of June through August. In the tropics, influenza
                                                                         treatment with the neuraminidase inhibitors should be
                        occurs year round with little seasonal variation.
                                                                         instituted within 48 hours of the onset of symptoms. Other
                                                                         tests such as direct fluorescent antibody and polymerase
                        Pathogenesis & Immunity
                                                                         chain reaction (PCR) are also used.
                        Influenza virus infection causes inflammation of the
                                                                           Influenza can also be diagnosed by the detection of anti-
                        mucosa of upper respiratory tract sites such as the nose and
                                                                         bodies in the patient’s serum. A rise in antibody titer of at
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