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Influenza virus entry and infection require host cell N-linked glycoprotein.

Chu VC, Whittaker GR.

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

A widely held view of influenza virus infection is that the viral receptor consists of cell surface carbohydrate sialic acid, which can be present as glycoprotein or glycolipid. Here, we examined influenza virus entry and infection in Lec1 cells, a mutant CHO cell line deficient in terminal N-linked glycosylation caused by a mutation in the N-acetylglucosaminyltransferase I (GnT1) gene. We show that influenza virus cannot infect Lec1 cells, despite having full capacity to undergo virus binding and fusion. Lec1 cells also show no virus replication defect, and infection was restored in Lec1 cells expressing wild-type GnT1. Viruses were apparently arrested at the level of internalization from the plasma membrane and were not endocytosed. Lec1 cells were refractory to infection by several strains of influenza virus, including H1 and H3 strains of influenza A, as well as influenza B virus. Finally, cleavage of N-glycans from wild-type CHO cells markedly reduced infection by influenza virus. We suggest that influenza virus specifically requires N-linked glycoprotein for entry into cells, and that sialic acid, although acting as an efficient attachment factor, is not sufficient as an influenza virus receptor in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15601777&dopt=Abstract flu, influenza



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Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria-pertussis-tetanus vaccines.

Nagai T, Suzuki Y, Kiyohara H, Susa E, Kato T, Nagamine T, Hagiwara Y, Tamura S, Yabe T, Aizawa C, Yamada H.

Oriental Medicine Research Center, The Kitasato Institute, 5-9-1 Shirokane, Minato-ku, 108-8642, Tokyo, Japan.

Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 microg) was intranasally (i.n.) inoculated with influenza vaccine (10 microg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3-14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 microg) was i.n. inoculated with the vaccine (10 microg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27-50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 microg) and influenza HA vaccine (1 microg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 microg) each and diphtheria-pertussis-tetanus (DPT) vaccine (10 microg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 microg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11535335&dopt=Abstract flu, influenza



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Nursing home outbreak of influenza A (H3N2): evaluation of vaccine efficacy and influenza case definitions.

Taylor JL, Dwyer DM, Coffman T, Groves C, Patel J, Israel E.

Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene, Baltimore 21201.

OBJECTIVES: Describe an outbreak of influenza A (H3N2); provide an analysis of vaccine efficacy; measure the sensitivity, specificity, and positive predictive value of 3 clinical case definitions of influenza. SETTING: A nursing home in Washington County, Maryland. The outbreak involved 52 residents (attack rate = 47.7%) and at least 10 of 140 employees (minimum attack rate = 7.1%). RESULTS: Twenty-five residents exhibited a 4-fold or greater increase in titer to influenza A/Sichuan/2/87. Vaccine efficacy was measured at -7.1%, suggesting that the influenza vaccine in 1988/1989 did not offer optimal protection against influenza A infection for the institutionalized elderly. CONCLUSIONS: The outbreak was a clear indicator of the need for rapid diagnosis. With the use of rapid diagnostic tests, influenza A could have been detected in time to use amantadine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1541810&dopt=Abstract flu, influenza



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Standardization and improvement of influenza surveillance: memorandum from a WHO/GEIG meeting.

[No authors listed]

The main objectives of influenza surveillance are early detection of influenza outbreaks and identification of the causative agent, collection and analysis of influenza morbidity and mortality data, and collection of influenza virus isolates and analysis of their antigenic characteristics. The true morbidity and mortality from influenza are difficult to estimate in most countries on the basis of only reports of influenza-like illnesses. Analysis and comparisons of the impact of influenza in different countries are also difficult because surveillance systems and methods vary from one country to another. This Memorandum describes generally applicable systems that could improve influenza surveillance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1568279&dopt=Abstract flu, influenza



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Update: influenza activity--United States and worldwide, and composition of the 1992-93 influenza vaccine.

[No authors listed]

During the 11 influenza seasons from 1977 through 1988, more than 10,000 excess deaths attributed to pneumonia and influenza (P&I) were reported during each of seven seasons, and approximately 45,000 deaths were reported during each of two seasons (CDC, unpublished data, 1992). The most important strategy for preventing influenza-associated morbidity and mortality is vaccination of persons in high-risk groups with vaccine closely matched to circulating strains. In collaboration with state and local health departments, CDC conducts surveillance to monitor influenza activity and to detect antigenic changes in the circulating strains of influenza virus. This report summarizes surveillance for influenza in the United States and worldwide during the 1991-92 season and describes the composition of the 1992-93 influenza vaccine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1569915&dopt=Abstract flu, influenza



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Translational control by influenza virus. Selective and cap-dependent translation of viral mRNAs in infected cells.

Garfinkel MS, Katze MG.

Department of Microbiology, School of Medicine, University of Washington, Seattle 98195.

In cells infected by influenza virus type A, host protein synthesis undergoes a rapid and dramatic shutoff. To define the molecular mechanisms underlying this selective translation, a transfection/infection protocol was developed utilizing viral and cellular cDNA clones. When COS-1 cells were transfected with cDNAs encoding nonviral genes and subsequently infected with influenza virus, protein expression from the exogenous genes was diminished, similar to the endogenous cellular genes. However, when cells were transfected with a truncated influenza viral nucleocapsid protein (NP-S) gene, the NP-S protein was made as efficiently in influenza virus infected cells as in uninfected cells, showing that the NP-S mRNA, although expressed independently of the influenza virus replication machinery, was still recognized as a viral and not a cellular mRNA. Northern blot analysis demonstrated that the selective blocks to nonviral protein synthesis were at the level of translation. Moreover, polysome experiments revealed that the translational blocks occurred at both the initiation and elongation stages of cellular protein synthesis. Finally, we utilized this transfection/infection system as well as double infection experiments to demonstrate that the translation of influenza viral mRNAs probably occurred in a cap-dependent manner as poliovirus infection inhibited influenza viral mRNA translation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1577765&dopt=Abstract flu, influenza



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An outbreak of influenza A (H3N2) in a well immunized nursing home population.

Coles FB, Balzano GJ, Morse DL.

Bureau of Communicable Disease Control, New York State Department of Health, Albany 12237.

OBJECTIVE: To describe the epidemiologic features of an outbreak of influenza A that occurred in a skilled nursing home although over 90 percent of the resident population had previously received influenza vaccine. DESIGN: Retrospective cohort study. SETTING: Skilled nursing home facility in western New York State. PATIENTS: Nursing home residents and patient-care staff. MAIN OUTCOME MEASURE: Incidence of influenza-like illness among vaccinated versus unvaccinated nursing home residents and staff. RESULTS: Thirty-seven of 124 residents (attack rate = 30%) and 18 of 146 staff (attack rate = 12%) had an influenza-like illness. Staff illness began 16 days prior to onset among residents. Six cases of pneumonia and three influenza-related deaths occurred, all among the vaccinated residents. Ninety percent of the nursing home residents and 10% of the staff received the influenza vaccine prior to the outbreak. The calculated vaccine efficacies were minus 21% and plus 45% for residents and staff, respectively. CONCLUSION: While antigenic drift of the circulating influenza virus was the major factor in the apparent vaccine failure, the observed poor staff immunization rate (10%) and absence of surveillance which precluded the use of amantadine chemoprophylaxis suggest that the use of these strategies may be of importance in controlling influenza outbreaks in nursing homes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1587976&dopt=Abstract flu, influenza



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Influenza deaths in Leicestershire during the 1989-90 epidemic: implications for prevention.

Nguyen-van-Tam JS, Nicholson KG.

Infectious Diseases Unit, Groby Road Hospital, Leicester.

There is an association between excess winter mortality and epidemics of influenza and it has been suggested that annual influenza vaccination should be offered to all over 65 years old as in the United States. This paper identifies the number of people dying from influenza in Leicestershire UK during the 1989-90 epidemic and the factors associated with a fatal outcome. The findings show that deaths attributed to influenza occur predominantly in very elderly people with underlying ill-health. The risk of influenzal death is greater in residential patients and increases substantially with the number of underlying medical conditions. The estimated death rates in vaccinated and non-vaccinated groups were not significantly different, but there were trends towards protection in both residential and non-residential groups. Influenza vaccine is not reaching the principal target groups and improved methods of influenza control are required.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1601083&dopt=Abstract flu, influenza



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Nucleotide sequence analysis of the HA1 coding portion of the haemagglutinin gene of swine H1N1 influenza viruses.

Neumeier E, Meier-Ewert H.

Abteilung fur Virologie, Institut fur Medizinische Mikrobiologie und Hygiene, Technische Universitat, Munchen, Germany.

The nucleotide and deduced amino acid sequences coding for the HA1 portion of the haemagglutinin (HA) genes of three swine influenza viruses were determined and compared with published HA sequence data for human H1N1 influenza viruses. Sequence differences between the classic swine influenza HAs sw37 (A/swine/29/37) and NJ76 (A/New Jersey/11/76) were randomly distributed in the molecule without being confined to antigenic sites. In contrast, sequence differences between the HAs of sw37 and the antigenically atypical strains sw38 (A/swine/Northern Ireland/38) and sw39 (A/swine/Cambridge/39) were clustered in hypervariable regions, similar to the pattern of changes that was present between sw37 and the human strains PR834 (A/PR/8/34) and WSN33 (A/WSN/33). Sequence homologies of the European swine influenza strains (sw38, sw39) were higher with the HAs of the human strains (PR834, WSN33) than with the classic swine influenza HAs (sw37, NJ76). Phylogenetic analysis showed that the HA genes of these two European swine influenza strains emerged from a different evolutionary lineage of H1 HAs than the HAs of classic swine influenza strains.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1604929&dopt=Abstract flu, influenza



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Antivirals for the chemoprophylaxis and treatment of influenza.

Van Voris LP, Newell PM.

Division of Infectious Diseases, Hamot Medical Center, Erie, PA.

Influenza virus infections are one of the leading causes of morbidity and mortality in the United States. Several antiviral agents, amantadine, rimantadine, and ribavirin, have been shown to be either therapeutically or prophylactically effective in influenza virus infections. Amantadine and rimantadine are effective, via the oral route, in treating and preventing influenza A infections. Aerosolized preparations of amantadine and rimantadine have also shown therapeutic efficacy against influenza A. Oral ribavirin has slight therapeutic efficacy in influenza A, but has also shown promising results in therapy of influenza B infections. Aerosolized ribavirin has also shown promise in treatment of patients who are severely ill with influenza A and B.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1609169&dopt=Abstract flu, influenza



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[Influenza in Poland in 1999]

[Article in Polish]

Kuszewski K, Brydak LB, Machala M.

Zaklad Epidemiologii Panstwowego Zakladu Higieny ul. Chocimska 24, 00-791 Warszawa.

A total of 2,344,773 cases of influenza were reported in Poland in 1999, corresponding to 6066.1 cases per 100,000 population and was 2.8 times higher as compared with 1998. The highest influenza incidence rate (10,770.9 per 100,000) was reported in Malopolskie voivodeship. Children up to 14 years old accounted for 34.9% (818,629; incidence 10,616.2 per 100,000) of all reported influenza cases. A total of 3,925 persons required hospitalization, eight times more as compared with 1998. The number of deaths due to influenza amounted to 402. Compared with 1998, in 1999 reported influenza deaths increased 6.4 times. During the second two weeks of January 1999 four influenza strains of type B were isolated from patients aged 13, 16, 31, and 38. During the first part of February 1999 another two strains of influenza virus type B were obtained from persons aged 35 and 45. All six isolates were related antigenically to the vaccine strain B/Beijing/184/93 and were confirmed by the WHO Collaborating Center for Influenza Reference and Research, London.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11556088&dopt=Abstract flu, influenza