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Effect of influenza B virus on nutrient transport in cultured epithelial cells.

Gurevitz M, Schulze IT, Swierkosz EM, Arens MQ, Schwarz KB.

Department of Pediatrics, Cardinal Glennon Children's Hospital, St. Louis, Missouri.

The possibility that influenza virus could induce changes in membrane permeability to nutrients ordinarily concentrated within the cell was examined. Madin-Darby canine kidney cells were infected with egg-grown influenza B virus at 37 degrees C and pH 7.4 (a condition in which influenza virus enters cells by endocytosis). Control cells were mock-infected with allantoic fluid from chick embryos. Transport of phosphate, 2-deoxyglucose, and alpha-aminoisobutyric acid was measured at various intervals, 0 to 10 hours after infection. Uptake of alpha-aminoisobutyric acid and phosphate by infected cells was inhibited at 2 hours as compared with controls, whereas at 6 to 10 hours, the uptake of all nutrients was higher in infected cells. Infected cells preloaded with phosphate or 2-deoxyglucose did not demonstrate increased release of these nutrients. Thus, the virally induced inhibition of uptake early in infection is not a consequence of loss of membrane integrity. Transport studies were also performed in cells with prebound virus exposed to pH 5.0 for 60 seconds at 37 degrees C and then incubated at pH 7.4, at 37 degrees C. Under these conditions, influenza A viruses are known to enter the cell membrane by fusing directly with it and to initiate cell to cell fusion as well. We demonstrated that influenza B virus also caused cell fusion under these conditions. In contradistinction to studies described above at pH 7.4, fused, infected cells demonstrated both marked release and diminished uptake of nutrients as compared with controls. We conclude that influenza B virus does have an effect on host cell membrane permeability; the type of effect seen is markedly influenced by factors known to determine mode of virus entry into the cell.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3695411&dopt=Abstract flu, influenza



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Possible association of mycoplasma and viral respiratory infections with bacterial meningitis.

Krasinski K, Nelson JD, Butler S, Luby JP, Kusmiesz H.

The presence of viral infection was evaluated in 160 children older than three months with bacterial meningitis who were admitted to Children's Medical Center or Parkland Memorial Hospital, Dallas, TX, between October 1979 and March 1982. Results were compared with a single serologic specimen in 138 children without meningitis. A recent history of upper respiratory infection was obtained from 60% of patients, including 10/13 with pneumococcal, 9/16 with meningococcal, and 77/131 with Haemophilus influenzae meningitis. Viral infection was documented by serologic response (23.8%) or viral isolation (13.2%) in 63/160 (40%) of patients with meningitis. There were 23 positive cultures (one patient with both adenovirus and respiratory syncytial virus). Picornaviruses, including two rhinoviruses, were isolated from six of the 24 subjects without meningitis who had viral cultures. There were 69 serologic conversions in meningitis patients, with 12 patients converting to two organisms and four patients converting to three organisms. Viral diagnoses included: adenovirus, 32 children; respiratory syncytial virus, 14; influenza A, 8; influenza B, 4; parainfluenza (1, 2, and 3), 12; picornaviruses, 9; herpes simplex virus, 1; and cytomegalovirus, 1. Additionally, 6/15 seroconverted to Mycoplasma pneumoniae. The acute geometric mean serum antibody titers of meningitis patients were lower than those of the comparison group for adenovirus (3.5 vs. 6.6, p less than or equal to 0.001) and influenza B (1.2 vs. 1.6, p less than or equal to 0.05). Twenty nine of 131 patients with H. influenzae had evidence of recent adenovirus infection. Primary infection with adenoviruses and possibly influenza B or mycoplasma precedes development of bacterial meningitis in some patients and may be a predisposing factor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3812456&dopt=Abstract flu, influenza



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Influenza virus infection induces functional alterations in peripheral blood lymphocytes.

Lewis DE, Gilbert BE, Knight V.

This report describes alterations in functional responses to lectin-induced stimulation of peripheral blood lymphocytes and in the natural killer cell (NKC) activity, of college students, obtained during an outbreak of influenza A/Philippines/2/82(H3N2) virus infection. These results are compared with similar observations in college students with an acute, febrile, noninfluenzal respiratory illness that occurred during the same outbreak. The lymphopenia typical of influenza during acute illness was shown to be due to a reduction in both T and B cells without alteration in the CD4:CD8 ratio. In addition, phytohemagglutinin and concanavalin A responses were reduced and NKC activity was increased, while pokeweed mitogen reactivity was unaltered at the time of admission to the study. Patients with noninfluenzal illness showed early polymorphonuclear leukocytosis and a similar lymphopenia. Lymphocyte functions were virtually unchanged during acute illness in noninfluenza patients. The relatively specific alterations in lymphocyte responses to lectin-induced stimulation in influenza patients may indicate that the peripheral T cells are incapable of activation via the CD3 or CD2 activation pathways. In addition, increased NKC activity in the periphery may be reflective of increased NKC activity in the lung. Influenza-infected individuals with higher NKC activity at the time of admission to the study also took longer to recover. Finally, the early lymphopenia and the later neutropenia in the influenza-infected patient may represent migration of these cells from the circulation to the infected respiratory tract as a consequence of infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2431043&dopt=Abstract flu, influenza



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Monovalent influenza A(H1N1) vaccine, 1986-1987. Recommendations of the Immunization Practices Advisory Committee. Centers for Disease Control, Department of Health and Human Services.

[No authors listed]

These supplemental recommendations provide guidelines for a monovalent influenza A(H1N1) vaccine for protection against a newly emerged variant of influenza that has recently caused outbreaks among children and young adults in Asia. Guidance is provided for the use of this monovalent vaccine, which contains 15 micrograms of A/Taiwan/1/86(H1N1) antigen, as a supplement to the standard trivalent influenza vaccine. Recommendations for the use of the standard trivalent influenza vaccine for the 1986-1987 season and the use of antivirals for the prevention and treatment of influenza remain in effect and should be referred to in conjunction with this supplemental recommendation. The trivalent vaccine is intended to protect against currently circulating strains of influenza A(H3N2) and influenza B viruses and may provide partial protection against the new influenza A(H1N1) variant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3021040&dopt=Abstract flu, influenza



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Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus.

Katze MG, DeCorato D, Krug RM.

During influenza virus infection, protein synthesis is maintained at high levels and a dramatic switch from cellular to viral protein synthesis occurs despite the presence of high levels of functional cellular mRNAs in the cytoplasm of infected cells (M. G. Katze and R. M. Krug, Mol. Cell. Biol. 4:2198-2206, 1984). To determine the step at which the block in cellular mRNA translation occurs, we compared the polysome association of several representative cellular mRNAs (actin, glyceraldehyde-3-phosphate dehydrogenase, and pHe7 mRNAs) in infected and uninfected HeLa cells. We showed that most of these cellular mRNAs remained polysome associated after influenza viral infection, indicating that the elongation of the proteins encoded by these cellular mRNAs was severely inhibited. Because the polysomes containing these cellular mRNAs did not increase in size but either remained the same size or decreased in size, the initiation step in cellular protein synthesis must also have been defective. Several control experiments established that the cellular mRNAs sedimenting in the polysome region of sucrose gradients were in fact associated with polyribosomes. Most definitively, puromycin treatment of infected cells caused the dissociation of polysomes and the release of cellular, as well as viral, mRNAs from the polysomes, indicating that the cellular mRNAs were associated with polysomes that were capable of forming at least a single peptide bond. A similar analysis was performed with HeLa cells infected by adenovirus, which also dramatically shuts down cellular protein synthesis. Again, it was found that most of the cellular mRNAs, which were translatable in reticulocyte extracts, remained associated with polysomes and that there was a combined initiation-elongation block to cellular protein synthesis. In cells infected by both adenovirus and influenza virus, influenza viral mRNAs were on larger polysomes than were several late adenoviral mRNAs with comparably sized coding regions. In addition, after influenza virus superinfection of cells infected by the adenovirus mutant dl331, a situation in which there is a limitation in the amount of functional initiation factor eIF-2 (M. G. Katze, B. M. Detjen, B. Safer, and R. M. Krug, Mol. Cell. Biol. 6:1741-1750, 1986), influenza viral mRNAs, but not late adenoviral mRNAs, were on polysomes. These results indicate that influenza viral mRNAs are better initiators of translation than are late adenoviral mRNAs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3023655&dopt=Abstract flu, influenza



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Influenza A among patients with human immunodeficiency virus: an outbreak of infection at a residential facility in New York City.

Fine AD, Bridges CB, De Guzman AM, Glover L, Zeller B, Wong SJ, Baker I, Regnery H, Fukuda K.

Communicable Disease Program, New York City Department of Health, Bronx, NY, USA. afine dohlan.cn.ci.nyc.ny.us

Although annual influenza vaccination is recommended for persons who are infected with human immunodeficiency virus (HIV), data are limited regarding the epidemiology of influenza or the effectiveness of influenza vaccination in this population. We investigated a 1996 outbreak of infection with influenza A at a residential facility for persons with AIDS. We interviewed 118 residents and employees, reviewed 65 resident medical records, and collected serum samples for measurement of influenza antibody titers. After controlling for history of smoking, influenza vaccination, and resident or employee status, in a multivariate model, HIV infection was not statistically associated with influenza-like illness (ILI). Symptoms and duration of ILI were similar for most HIV-infected and HIV-uninfected persons. However, 8 (21.1%) of 38 HIV-infected persons with ILI (vs. none of 15 HIV-uninfected persons) were either hospitalized, evaluated in an emergency room, or had ILI lasting > or = 14 days (P=.06). Vaccination effectiveness (VE) was similar for HIV-infected and HIV-uninfected persons. Vaccination was most effective among HIV-infected persons with CD4 cell counts of >100 cells/microL (VE, 65%; 95% CI, 36%--81%) or HIV type 1 virus load of <30,000 copies/mL (VE, 52%; 95% CI, 11%--75%). Providers should continue to offer influenza vaccination to HIV-infected persons.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11360221&dopt=Abstract flu, influenza



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Cell-mediated immune responses to influenza virus antigens expressed by vaccinia virus recombinants.

Andrew ME, Coupar BE, Ada GL, Boyle DB.

Department of Microbiology, John Curtin School of Medical Research, Australian National University, Canberra, A.C.T.

Recombinant vaccinia viruses enable studies of immune recognition of antigens expressed from single viral genes. We have constructed recombinants expressing the haemagglutinin (HA) and nucleoprotein (NP) genes of the influenza virus A/PR/8/34 (H1N1). These recombinant viruses together with a recombinant expressing the HA from influenza virus A/JAP/305/57 (H2N2) have been used to examine the cytotoxic T lymphocyte (CTL) response to these influenza virus antigens. Both antigens are recognised by murine CTL and recognition of HA is influenza virus subtype-specific, whereas recognition of NP is crossreactive. In limiting dilution studies approximately 10% of the influenza CTL response is HA-specific, while approximately 30% of the response is NP-specific. Despite the ability of NP to stimulate a significant CTL response, mice immunised with the NP-vaccinia recombinant are not as well protected from subsequent lethal challenge with influenza virus, as mice immunised with the HA vaccinia recombinant. These studies demonstrate that viral antigens expressed from vaccine recombinants can provide protective immunity and that the influenza-poxvirus recombinants can provide data on protective immunity generated by individual viral proteins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3509883&dopt=Abstract flu, influenza



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Time-resolved fluoroimmunoassay with monoclonal antibodies for rapid diagnosis of influenza infections.

Walls HH, Johansson KH, Harmon MW, Halonen PE, Kendal AP.

Monoclonal antibodies that are broadly reactive with either influenza A or influenza B viruses were used to develop a 2- to 3-h antigen capture time-resolved fluoroimmunoassay (TR FIA) for detecting influenza viral antigens in both original nasopharyngeal aspirate specimens and in tissue cultures inoculated with nose or throat swab specimens. The lower limit of sensitivity of the assay was about 10 pg of protein as determined with purified influenza A nucleoprotein expressed by recombinant DNA. When the TR FIA was performed with 96 nasopharyngeal aspirate specimens collected during outbreaks of influenza A (H3N2) virus and the results were compared with serodiagnosis results with paired sera, the specificity and sensitivity of TR FIA for the demonstration of influenza A infections were 95 and 85%, respectively. In culture confirmation assays, more than 80% of the swab specimens that grew influenza A or B virus within 7 days could be identified by the TR FIA within 48 h of the inoculation of cells. The results are consistent with those previously reported for respiratory syncytial virus and extend the applicability of monoclonal antibody-based TR FIA for the rapid diagnosis of acute respiratory viral infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3537001&dopt=Abstract flu, influenza



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Response to influenza immunisation during treatment for cancer.

Chisholm JC, Devine T, Charlett A, Pinkerton CR, Zambon M.

Children's Unit, Royal Marsden Hospital, Down's Rd, Sutton, Surrey SM2 5PT, UK. julia.chisholm gosh-tr.nthames.nhs.uk

AIMS: To assess the annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children. METHODS: Eighty four children with cancer were tested for susceptibility to the circulating strains of influenza virus in autumn 1995 and 1996. Non-immunised children were reassessed the following spring for serological evidence of natural infection. Forty two patients received two doses of influenza vaccine. These children were receiving continuing chemotherapy for acute lymphoblastic leukaemia or were within six months of completing chemotherapy. RESULTS: Among the 84 children tested for influenza virus susceptibility only 8% of patients were fully protected (antibody titres >/= 40) against all three of the prevalent influenza virus strains; 33% were susceptible to all three viruses. Evidence of acquired natural infection was seen in 30% of unimmunised patients. Among immunised susceptible patients, 66% made some protective response to the vaccine and 55% showed protective antibody titres to all three viral strains following vaccination. Older age was associated with increased response to the H1N1 and H3N2 vaccine components, but total white cell count or neutrophil count at immunisation, type of cancer, or length of time on treatment for acute lymphoblastic leukaemia did not affect response. CONCLUSIONS: Most children with cancer studied were at risk of influenza infection. A significant response to immunisation was seen, supporting annual influenza vaccination for children being treated for cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11369567&dopt=Abstract flu, influenza



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Subtype-specific identification of influenza virus in cell cultures with FITC labelled egg yolk antibodies.

Doller PC, Doller G, Gerth HJ.

We report on results obtained with a direct immunofluorescence test for subtype-specific identification of influenza virus in detached cells of MDCK cultures after inoculation of 281 clinical specimens from patients with influenza-like disease. Influenza virus antibodies were produced in eggs from immunized hens and labelled with FITC. In 157 cases CPE was found in MDCK cells. A total of 57 cases of influenza A (H3N2), 86 cases of influenza A (H1N1), and 14 cases of influenza B were identified. In 33 cases of influenza A (H1N1) infection with massive CPE guinea pig but not chicken erythrocytes were agglutinated by the cell culture supernatants. The single step immunofluorescence test described proved easy to perform and results were obtained within 1 h after CPE was observed in contrast to the conventional HIT which is very time-consuming.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3547056&dopt=Abstract flu, influenza



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Serological evidence of recent influenza virus A (H 3 N 2) infections in forensic cases of the sudden infant death syndrome (SIDS).

Zink P, Drescher J, Verhagen W, Flik J, Milbradt H.

40 forensic SIDS cases were found to have a significantly higher rate of serologic evidence of recent influenza A (H 3 N 2) infection than did matched controls. In contrast, the SIDS cases had serologically no significantly increased infection rate with influenza H 1 N 1 and B virus, parainfluenza virus, RS virus, adenovirus, and cytomegalovirus. SIDS cases with recent influenza infection had a significantly higher rate of histological findings as described for primary viral pneumonia than did SIDS cases without influenza infection. SIDS cases with recent influenza infection occurred much more frequently during epidemic than during interepidemic influenza A (H 3 N 2) periods. Our results confirm previous reports that SIDS cases have an increased rate of respiratory virus infections. However, they cannot prove a causal relationship between influenza infection and death. Since our SIDS cases comprised 75 per cent of cases aged more than three months, our results pertain essentially to cases of this age group.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3548651&dopt=Abstract flu, influenza