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Neutrophil interaction with influenza-infected epithelial cells.

Ratcliffe DR, Nolin SL, Cramer EB.

Department of Anatomy and Cell Biology, State University of New York Health Science Center, Brooklyn 11203.

An in vitro model system was used to study the early neutrophil response to influenza-infected epithelia. In the absence of serum, neutrophil adherence to influenza-infected confluent monolayers of Madin-Darby canine kidney epithelial cells (MDCK) was approximately 590 times greater than neutrophil binding to control cultures. The leukocytes bound specifically to virus-infected cells. Neutrophil adherence to influenza-infected MDCK cells was monitored during the course of one replication cycle, and binding began at a time (4.5 hours) that coincided with viral protein insertion in the apical cell membrane. Ultrastructural examination at 4.5 hours showed that greater than 90% of the neutrophils adhered to the epithelial cell membrane in the absence of budding virus and, at 6.5 hours, 100% of the neutrophils adhered to the epithelium with emerging virions. The number of neutrophils bound to influenza-infected MDCK cells was not affected by the presence or absence of calcium or magnesium but did depend on the amount of viral inoculum and on the temperature of the culture. In direct contrast to hemadsorption of RBCs, neutrophil binding to influenza-infected MDCK cells was 100% greater at 37 degrees C than at 4 degrees C. The neutrophil surface molecules that bound influenza virus appeared to become functionally polarized because the adherence of neutrophils to budding influenza virus or to a virus-coated surface inhibited the neutrophils from binding additional influenza virus to their nonadherent surface.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3390606&dopt=Abstract flu, influenza



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Influenza and human immunodeficiency virus infection: absence of HIV progression after acute influenza infection.

Golden MP, Sajjad Z, Elgart L.

Departments of Medicine and Infectious Diseases, Hospital of Saint Raphael, and Yale University School of Medicine, New Haven, CT 06511, USA. mgolden srhs.org

Influenza is a major cause of morbidity for people with significant underlying disease, but the impact of influenza on people infected with human immunodeficiency virus (HIV) remains unclear. We studied a population of HIV-infected adults during the 1998-1999 influenza season to see whether influenza had any adverse effects on the course of HIV infection. During 5 months of follow-up, we found no unique clinical manifestations or negative impact on CD4(+) cell count, virus load, or clinical progression of HIV disease. Although half of our cohort received antibiotic therapy, none received specific anti-influenza therapy and none required hospitalization. Acute influenza does not appear to be a risk for progression of HIV disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11303274&dopt=Abstract flu, influenza



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The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian-human influenza A/Pintail/79 reassortant viruses for monkeys.

Snyder MH, Buckler-White AJ, London WT, Tierney EL, Murphy BR.

Reassortant viruses which possessed the hemagglutinin and neuraminidase genes of wild-type human influenza A viruses and the remaining six RNA segments (internal genes) of the avian A/Pintail/Alberta/119/79 (H4N6) virus were previously found to be attenuated in humans. To study the genetic basis of this attenuation, we isolated influenza A/Pintail/79 X A/Washington/897/80 reassortant viruses which contained human influenza virus H3N2 surface glycoprotein genes and various combinations of avian or human influenza virus internal genes. Twenty-four reassortant viruses were isolated and first evaluated for infectivity in avian (primary chick kidney [PCK]) and mammalian (Madin-Darby canine kidney [MDCK]) tissue culture lines. Reassortant viruses with two specific constellations of viral polymerase genes exhibited a significant host range restriction of replication in mammalian (MDCK) tissue culture compared with that in avian (PCK) tissue culture. The viral polymerase genotype PB2-avian (A) virus, PB1-A virus, and PA-human (H) virus was associated with a 900-fold restriction, while the viral polymerase genotype PB2-H, PB1-A, and PA-H was associated with an 80,000-fold restriction of replication in MDCK compared with that in PCK. Fifteen reassortant viruses were subsequently evaluated for their level of replication in the respiratory tract of squirrel monkeys, and two genetic determinants of attenuation were identified. First, reassortant viruses which possessed the avian influenza virus nucleoprotein gene were as restricted in replication as a virus which possessed all six internal genes of the avian influenza A virus parent, indicating that the nucleoprotein gene is the major determinant of attenuation of avian-human A/Pintail/79 reassortant viruses for monkeys. Second, reassortant viruses which possessed the viral polymerase gene constellation of PB2-H, PB1-A, and PA-H, which was associated with the greater degree of host range restriction in vitro, were highly restricted in replication in monkeys. Since the avian-human influenza reassortant viruses which expressed either mode of attenuation in monkeys replicated to high titer in eggs and in PCK tissue culture, their failure to replicate efficiently in the respiratory epithelium of primates must be due to the failure of viral factors to interact with primate host cell factors. The implications of these findings for the development of live-virus vaccines and for the evolution of influenza A viruses in nature are discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2441080&dopt=Abstract flu, influenza



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[The nature of the influenza C virus receptor and the specificity of the receptor-destroying enzyme]

[Article in Russian]

Herrler G, Schauer J, Rott R, Klenk HD.

Bacterial neuraminidases destroy influenza C virus receptors of chick erythrocytes and inactivate hemagglutination inhibitors: rat alpha 1-macroglobulin (RMG) and bovine submaxillary mucin (BSM). These data indicate that neuraminic acid may be a component of influenza C virus receptor. The inhibiting activity of RMG and BSM is also eliminated by the receptor-destroying enzyme (RDE) of influenza C virus. After inactivation, the inhibitors (RMG and BSM) contain a reduced amount of N-acetyl-9-0-acetylneuraminic acid (Neu5, 9Ac2) and a larger amount of N-acetylneuraminic acid (Neu5 Ac). Transformation of Neu5, 9Ac2 into Neu5 Ac may also occur upon incubation of free neuraminic acid with influenza C virus. These data indicate that the RDE of influenza C virus is neuraminate-O-acetylesterase (N-acyl-9 4-O-acetylneuraminate O-acetylhydrolase (EC 3.1.1.53). It was shown that inhibition of influenza C virus hemagglutination by RMG and BSM and, apparently, adhesion of the virus to the cell surface involves binding of influenza C virus with Neu5, 9Ac2.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2445106&dopt=Abstract flu, influenza



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Surveillance of respiratory viral infections by rapid immunofluorescence diagnosis, with emphasis on virus interference.

Anestad G.

During the 7-year period from September 1978 to August 1985, smear specimens of nasopharyngeal secretions from 3132 patients mainly hospitalized children, taken in different regions in Norway, were examined for respiratory viruses by the rapid immunofluorescence (IF) technique. A positive diagnosis for respiratory syncytial virus (RSV), parainfluenza virus type 1, 2 and 3 or influenza A and B virus was made for 896 patients (29%). The greatest prevalence for all these viruses was observed during the colder months with only sporadic cases during the summer months. A relative increase in parainfluenza virus activity, involving several parainfluenza virus types, was observed in every second autumn and during these periods only sporadic cases of RSV infection were diagnosed. Also both RSV and parainfluenza viruses were less frequently found during influenza virus epidemics and regional differences in RSV activity were observed. During the four autumn periods 1982-85 the monthly number of positive virus identifications by IF followed an epidemic curve, while the corresponding number of negative samples was relatively constant. The results of this study suggest interference between RSV, parainfluenza viruses and influenza virus in reaching their epidemiological peaks. It is suggested that interferon might be a mediator of this effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2824225&dopt=Abstract flu, influenza



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The human and murine influenza-specific B cell repertoires share a common idiotope.

Sigal NH, Chan M, Reale MA, Moran T, Beilin Y, Schulman JL, Bona C.

We have dissected the human influenza-specific B cell repertoire by performing Epstein-Barr virus (EBV) limiting dilution analysis of lymphocytes obtained from donors before and after immunization with a commercially available influenza vaccine. In addition to an analysis of precursor frequency and light chain diversity, we studied sera and culture supernatants containing human anti-influenza antibodies with a panel of murine monoclonal antibodies specific for idiotopes identified on murine anti-PR8 and anti-X-31 antibodies. An idiotypic specificity present on the X-31-specific murine monoclonal PY206 has previously been shown to be shared by murine antibodies specific for PR8, X-31, and other influenza viruses. We observed little correlation among the following parameters: anti-viral titer, serum idiotope content, precursor frequency and immune status. More interestingly, there was a striking predominance of human influenza-specific antibodies that utilized lambda light chains. In addition, 12 of 26 human anti-influenza monoclonals strongly inhibited the binding of one of the murine anti-idiotopes to the labeled murine antibody, PY206. This is the same idiotope that is shared among murine antiinfluenza antibodies and all six individuals studied contained clones reactive with this anti-idiotope. Seven of these 12 idiotope-positive human antibodies gave partial cross-reactivity in a second anti-idiotypic system. These observations imply that a significant level of homology exists between the binding sites of human and murine influenza-specific antibodies and suggest that idiotypic manipulation of the human immune response to influenza virus may have important therapeutic implications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3114381&dopt=Abstract flu, influenza



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Influenza A and B virus IgG and IgM serology by enzyme immunoassays.

Koskinen P, Vuorinen T, Meurman O.

Enzyme immunoassays (EIA) for IgG and IgM antibodies against influenza A and B virus are described. One hundred and seven subjects with a clinical diagnosis of acute respiratory infection (influenza, bronchitis or pneumonia) were selected for this study during two epidemics of influenza A which occurred in Finland in 1983 and 1985. Paired sera and nasopharyngeal secretions were obtained from all subjects. The sera were tested for influenza A and B antibodies by IgG and IgM EIAs and by complement fixation tests. The nasopharyngeal secretions were tested by an indirect EIA for influenza A and B antigens. The IgG EIA was found to be better than complement fixation for the diagnosis of influenza A infections: only 22% of the significant increases detected by this test were also positive by complement fixation. The additional contribution of the IgM EIA to the number of positives was minimal. It was also found that testing a single 1/1000 dilution of serum for influenza A and 1/100 dilution for influenza B in the IgG EIA gave as many positives as the conventional method of testing several dilutions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3301380&dopt=Abstract flu, influenza



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Synthesis and cellular location of the ten influenza polypeptides individually expressed by recombinant vaccinia viruses.

Smith GL, Levin JZ, Palese P, Moss B.

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

A complete set of recombinant vaccinia viruses that express each of the influenza virus polypeptides has been constructed. PB1, PB2, PA, HA, NP, M1, and NS1 genes were derived from influenza virus A/PR/8/34, NA from influenza virus A/Cam/46, and M2 and NS2 genes from influenza virus A/Udorn/72. Cells infected with these recombinant viruses synthesize influenza polypeptides that are precipitable with specific antisera and that have electrophoretic mobilities similar to the corresponding influenza virus polypeptides. Indirect immunofluorescence studies have shown that HA, NA, and MS2 proteins migrate to the cell surface; PB2, PB1, PA, NP, and NS1 proteins migrate to the cell nucleus; and M1 and NS2 are distributed throughout the cell, although NS2 accumulates preferentially in nuclei. These transport processes occurred independently of other influenza polypeptides and are therefore attributable to the intrinsic properties of the influenza polypeptides themselves.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3310381&dopt=Abstract flu, influenza



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[Reduction of medical resources utilization by influenza vaccination for hospitalized elderly patients]

[Article in Japanese]

Hara Y, Ikematsu H, Nabeshima A, Hagiwara A, Nobutomo K, Kashiwagi S.

Department of Health Services Management and Policy, Graduate School of Medicine, Kyushu University.

In order to evaluate the economic efficacy of influenza vaccination for the elderly inpatients, we have investigated the health insurance fee of elderly inpatients in Japan. It was revealed that the health insurance fee varied by patients largely, ranging from 7,000 yen to 90,000 yen. Primary reason of this variation was due to the existence of the same effective drugs with variant prices and there were no rules concerning the period of drug medication. Thus, it was found that it would be improper to use the medication fee as a measure in evaluating the effects of influenza vaccinations. In this study, we used the length of days of testing and medication such as oral antibiotics, blood cell count, etc. as a measure to evaluate the effect of influenza vaccination. We compared these measures among elderly hospitalized patients with influenza vaccination or without influenza vaccination by ADL. Mean length of days of oral antibiotics was 2.64 (+/- 6.40) days for those with vaccination, and 3.92 (+/- 7.31) days for those without vaccination. Mean length of days of injection antibiotics was 2.52 (+/- 5.53) days for those with vaccination, and 8.82 (+/- 15.1) days for those without vaccination. Mean length of days of cells blood counter was 2.63 (+/- 2.22) days for those with vaccination, and 4.44 (+/- 3.20) days for those without vaccination. Mean length of days of chest X-ray was 1.30 (+/- 2.07) days for those with vaccination, and 2.56 (+/- 3.49) days for those without vaccination. These results suggest that influenza vaccination reduces medical utilization of resources. It was also revealed that influenza vaccination is most effective when elderly patients who are bed-bound are vaccinated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11321777&dopt=Abstract flu, influenza