Showing papers on "Influenza A virus published in 1988"
TL;DR: The monoclonal antibody, when included in a plaque assay overlay, considerably showed the growth of some influenza virus strains and is a specific effect for the M2 antibody as determined by an analysis of recombinants with defined genome composition and by the observation that competition by an N-terminal peptide prevents the antibody restriction of virus growth.
Abstract: The influenza A virus M2 protein is an integral membrane protein of 97 amino acids that is expressed at the surface of infected cells with an extracellular N-terminal domain of 18 to 23 amino acid residues, an internal hydrophobic domain of approximately 19 residues, and a C-terminal cytoplasmic domain of 54 residues. To gain an understanding of the M2 protein function in the influenza virus replicative pathway, we produced and characterized a monoclonal antibody to M2. The antibody-binding site was located to the extracellular N terminus of M2 as shown by the loss of recognition after proteolysis at the infected-cell surface, which removes 18 N-terminal residues, and by the finding that the antibody recognizes M2 in cell surface fluorescence. The epitope was further defined to involve residues 11 and 14 by comparing the predicted amino acid sequences of M2 from several avian and human strains and the ability of the M2 protein to be recognized by the antibody. The M2-specific monoclonal antibody was used in a sensitive immunoblot assay to show that M2 protein could be detected in virion preparations. Quantitation of the amount of M2 associated with virions by two unrelated methods indicated that in the virion preparations used there are 14 to 68 molecules of M2 per virion. The monoclonal antibody, when included in a plaque assay overlay, considerably showed the growth of some influenza virus strains. This plaque size reduction is a specific effect for the M2 antibody as determined by an analysis of recombinants with defined genome composition and by the observation that competition by an N-terminal peptide prevents the antibody restriction of virus growth.
551 citations
TL;DR: Results suggest that, like influenza C viruses, human coronav virus OC43 and bovine coronavirus recognize O-acetylated sialic acid or a similar derivative as cell receptor.
Abstract: Human coronavirus OC43 and bovine coronavirus elute from agglutinated chicken erythrocytes when incubated at 37 degrees C, suggesting the presence of a receptor-destroying enzyme. Moreover, bovine coronavirus exhibits an acetylesterase activity in vitro using bovine submaxillary mucin as substrate similar to the enzymatic activity found in influenza C viruses. Furthermore, pretreatment of erythrocytes with either influenza C virus or bovine coronavirus eliminates subsequent binding and agglutination by either coronaviruses or influenza C virus, whereas binding of influenza A virus remains intact. In addition, hemagglutination by coronaviruses can be inhibited by pretreatment of erythrocytes with Arthrobacter ureafaciens or Clostridium perfringens neuraminidase or by addition of sialic acid-containing gangliosides. These results suggest that, like influenza C viruses, human coronavirus OC43 and bovine coronavirus recognize O-acetylated sialic acid or a similar derivative as cell receptor.
333 citations
TL;DR: The HA gene from a virulent H5 influenza virus was expressed in mammalian cells, and the cleavage site of the HA was explored by using site-specific mutagenesis to establish that most of the basic amino acids at this site are critical for cleavage activation.
Abstract: Cleavage of the hemagglutinin (HA) in tissue culture systems has been correlated with virulence of avian influenza viruses. To examine the structural requirements for cleavage of the HA, the HA gene from a virulent H5 influenza virus was expressed in mammalian cells (CV-1), and the cleavage site of the HA was explored by using site-specific mutagenesis. The expressed HA protein exhibited normal cleavage, transport to the cell membrane, and ability to adsorb and to fuse erythrocytes at pH 5. Site-specific mutagenesis of the HA directly established that (i) most of the basic amino acids at this site are critical for cleavage activation; (ii) besides the connecting peptide sequence, at least one other structural feature of the HA is required for enzyme recognition; and (iii) the length of the connecting peptide can abrogate the structural feature(s).
259 citations
TL;DR: To define the nuclear signal of the NS1 protein, a series of recombinant simian virus 40 vectors that express deletion mutants or fusion proteins was constructed and resulted in identification of two regions of theNS1 protein which affect its cellular location.
Abstract: The NS1 protein of influenza A virus has been shown to enter and accumulate in the nuclei of virus-infected cells independently of any other influenza viral protein. Therefore, the NS1 protein contains within its polypeptide sequence the information that codes for its nuclear localization. To define the nuclear signal of the NS1 protein, a series of recombinant simian virus 40 vectors that express deletion mutants or fusion proteins was constructed. Analysis of the proteins expressed resulted in identification of two regions of the NS1 protein which affect its cellular location. Nuclear localization signal 1 (NLS1) contains the stretch of basic amino acids Asp-Arg-Leu-Arg-Arg (codons 34 to 38). This sequence is conserved in all NS1 proteins of influenza A viruses, as well as in that of influenza B viruses. NLS2 is defined within the region between amino acids 203 and 237. This domain is present in the NS1 proteins of most influenza A virus strains. NLS1 and NLS2 contain basic amino acids and are similar to previously defined nuclear signal sequences of other proteins.
209 citations
TL;DR: The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans.
Abstract: Clinical studies previously demonstrated that live influenza A virus vaccines derived by genetic reassortment from the mating of influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus with epidemic wild-type influenza A viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. These influenza A reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, but the genes of the ca virus parent which specify the ca, ts, and attenuation (att) phenotypes have not adequately been defined. To identify the genes associated with each of these phenotypes, we isolated six single-gene substitution reassortant viruses, each of which inherited only one RNA segment from the ca parent virus and the remaining seven RNA segments from the A/Korea/1/82 (H3N2) wild-type virus parent. These were evaluated in vitro for their ca and ts phenotypes and in ferrets, hamsters, and seronegative adult volunteers for the att phenotype. We found that the polymerase PA gene of the ca parent specifies the ca phenotype and that the PB2 and PB1 genes independently specify the ts phenotype. The PA, M, PB2, and PB1 genes of the ca donor virus each contribute to the att phenotype. The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans.
166 citations
Journal Article•
TL;DR: Influenza virus causes neutrophil activation leading to significant perturbations in Ca2+ metabolism and later to impaired mobilization of Ca2- stores, which offers a model for phagocyte deactivation and an opportunity to define control mechanisms of signal transduction.
Abstract: Bacterial superinfection in influenza A virus-related illness may in part be explained by virus-induced neutrophil dysfunction. We here provide evidence that this effect is related to abnormal calcium metabolism of virus-infected cells. Neutrophils exposed to influenza virus for 0.5 h at 37 degrees C showed depressed O2- generation and release of radiolabeled arachidonic acid upon stimulation with FMLP. The peak cytosolic Ca2+ level achieved by virus-infected neutrophils after FMLP stimulation was significantly depressed as is efflux of 45Ca2+. This deficient Ca2+ mobilization could not be attributed to alterations of inositol phosphate production or Ca2+ influx in response to FMLP, both of which were unaffected by prior virus infection. Given these findings, the immediate effects of influenza virus on neutrophil Ca2+ metabolism were examined. The virus itself caused a rise in cytosolic Ca2+ and an efflux of 45Ca2+ without any corresponding 45Ca2+ influx. Total cell Ca2+ however was not depleted as measured by atomic absorption. Influenza virus, therefore, causes neutrophil activation leading to significant perturbations in Ca2+ metabolism and later to impaired mobilization of Ca2+ stores. This system offers a model for phagocyte deactivation and an opportunity to define control mechanisms of signal transduction.
120 citations
TL;DR: Chickens vaccinated with isolated N2 in adjuvant or with inactivated H5N2 influenza virus were protected from clinical signs and death after challenge with A/Ck/Penn/1370/83 influenza virus, but these animals were completely susceptible and died of infection with a heterologous subtype of influenza virus.
115 citations
TL;DR: Human influenza pandemics commonly arise by genetic reassortment between human and avian viruses in pigs, yet global developments in aquaculture — the so-called 'Blue Revolution' — will mean increased colocation of people, ducks and pigs.
Abstract: Human influenza pandemics commonly arise by genetic reassortment between human and avian viruses in pigs. Yet global developments in aquaculture--the so-called 'Blue Revolution'--will mean increased co-location of people, ducks and pigs.
114 citations
TL;DR: Findings indicate that these H3 viruses may have been introduced into pigs from ducks, or an early human H3 virus was introduced into the pig population where the virus accumulated substantial mutations.
107 citations
TL;DR: The benefits of influenza vaccination are illustrated and the use of amantadine hydrochloride at a dosage of 100 mg daily for outbreak control among elderly persons is supported.
Abstract: • An outbreak caused by influenza A/Philippines/2/82 (H3N2)—like viruses occurred in a partially vaccinated nursing home population in January 1985. During the first six days of the outbreak, 14 (25%) of 55 residents developed influenzalike illness. The risk of illness was most strongly associated with undetectable levels of antibody against the epidemic strain, with unvaccinated case-patients having more severe illnesses and a higher rate of hospitalization than vaccinated case-patients (5/8 vs 0/6). During the period of amantadine hydrochloride prophylaxis (100 mg/d) from days 7 to 35, only two (5%) of the remaining 41 residents became ill, even though 11 (27%) had no detectable antibody. Serum amantadine levels obtained on day 35 ranged from 117 to 737 ng/mL (mean 309 ng/mL), similar to therapeutic levels documented in younger adults who have taken the standard regimen of 200 mg/d; there were few clinically significant side effects. These findings illustrate the benefits of influenza vaccination and support the use of amantadine hydrochloride at a dosage of 100 mg daily for outbreak control among elderly persons. (Arch Intern Med1988;148:865-868)
106 citations
TL;DR: Investigations of the structure, intracellular transport, and biological activities of the mutant hemagglutinin molecules indicated that supernumerary carbohydrate side chains can be used to shield or disrupt functional epitopes on the surface of hemag GLU, and the presence of an additional oligosaccharide may cause temperature-dependent defects in the transport of the glycoprotein.
Abstract: We have constructed and expressed a series of mutant influenza virus hemagglutinins, each containing a new consensus site for glycosylation in addition to the seven sites found on the wild-type protein. Oligosaccharide side chains were added with high efficiency at four of the five novel sites, located on areas of the protein's surface that are not normally shielded by carbohydrate. Investigations of the structure, intracellular transport, and biological activities of the mutant hemagglutinin molecules indicated that (a) supernumerary carbohydrate side chains can be used to shield or disrupt functional epitopes on the surface of hemagglutinin, and (b) the presence of an additional oligosaccharide may cause temperature-dependent defects in the transport of the glycoprotein. We discuss the addition of supernumerary oligosaccharides as a general tool for shielding chosen areas of the surface of proteins that enter or traverse the secretory pathway.
TL;DR: The duration of immunity as measured by virological, serological and clinical responses following infection with influenza A/equine/Newmarket/79 (H3N8) was assessed in repeated challenge experiments in which ponies were infected by exposure to aerosols of infectious virus.
Abstract: The duration of immunity as measured by virological, serological and clinical responses following infection with influenza A/equine/Newmarket/79 (H3N8) was assessed in repeated challenge experiments in which ponies were infected by exposure to aerosols of infectious virus. Previous infection stimulated complete clinical protection which persisted for at least 32 weeks as demonstrated by the absence of febrile responses and coughing in two groups of ponies infected 16 weeks or 32 weeks after the first infection. Partial clinical protection persisted for over a year as demonstrated by the absence of coughing and a reduction in the number of febrile responses in a group of ponies infected 62 weeks after their first infection. These results contrasted with those observed in immunologically naive control ponies which developed pyrexia, dyspnoea and nasal discharge and coughing. The kinetics of virus specific antibody production in primary and secondary infections with equine influenza were studied by the single radial haemolysis test and a radioisotopic antiglobulin binding assay which measured virus specific IgGab antibody isotype. Antibody to the haemagglutinin, as measured by the single radial haemolysis test, declined rapidly after primary infection whereas the IgGab responses to whole virus antigens persisted for longer. The single radial haemolysis test was therefore particularly useful for the detection of antibody responses in multiple infections or exposures to influenza antigens. The radioisotopic antiglobulin binding assay was more sensitive for identifying infections which had occurred more than six months previously, as evidenced by anamnestic IgGab responses in ponies with low levels of antibody before rechallenge.
TL;DR: In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus‐specific Tc cell responses.
Abstract: Primary immunization with a single inoculum of either micelles or iscoms containing influenza A virus glycoproteins failed to induce either B or cytotoxic T (Tc) cell responses. In contrast, immunization with two inocula of iscoms, but not micelles, resulted in the appearance of influenza virus-specific antibody-secreting cells (ASC) but not Tc cells in the lung. There was a 10-fold increase in Tc cell precursor frequency and an increase in ASC generated by secondary in vitro stimulation of lung cell cultures obtained from mice primed with iscoms but not micelles. In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus-specific Tc cell responses. In contrast homologous virus challenge failed to induce detectable secondary B or Tc cell responses.
TL;DR: The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness, and the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.
Abstract: The infectivity, immunogenicity, and efficacy of live, attenuated influenza A/Texas/1/85 (H1N1) and A/Bethesda/1/85 (H3N2) avian-human (ah) and cold-adapted (ca) reassortant vaccines were compared in 252 seronegative adult volunteers. The immunogenicity and efficacy of the H1N1 reassortant vaccine were also compared with those of the trivalent inactivated virus vaccine. Each reassortant vaccine was satisfactorily attenuated. The 50% human infectious dose was 10(4.9) for ca H1N1, 10(5.4) for ah H1N1, 10(6.4) for ca H3N2, and 10(6.5) TCID50 for ah H3N2 reassortant virus. Within a subtype, the immunogenicities of ah and ca vaccines were comparable. Five to seven weeks after vaccination, volunteers were challenged with homologous wild-type influenza A virus. The magnitude of shedding of virus after challenge was greater than 100-fold less in H1N1 vaccinees and greater than 10-fold less in H3N2 vaccinees compared with unimmunized controls. The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness. Thus, the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.
TL;DR: It is suggested that, upon B-cell surface immunoglobulin-antigen interaction and uptake of intact virus, B cells specific for viral surface proteins process and present all major structural viral antigens, enabling the B cells to interact with TH clones specific for any virion protein.
Abstract: When a helper T-cell (TH) clone specific for the hemagglutinin, neuraminidase, matrix protein, or nucleoprotein of influenza strain A/PR/8/34 is adoptively transferred to athymic mice 1 day after virus infection the anti-viral antibody response of the mouse is enhanced. This response is directed predominantly to the hemagglutinin and requires associative T-cell-B-cell interactions. Delaying transfer of the TH clone has three consequences: (i) the onset of the anti-hemagglutinin antibody response is delayed; (ii) the titer of the anti-hemagglutinin response is reduced; and (iii) the titer of the antibody in the response against the internal proteins, matrix protein and nucleoprotein, is enhanced upon transfer of matrix protein- or nucleoprotein-specific, but not hemagglutinin- or neuraminidase-specific, TH clones. Thus, there is a hierarchy of help: B cells recognizing viral surface components, hemagglutinin or neuraminidase, can receive help from TH clones specific for any of the major structural viral proteins. In contrast, B cells responding to internal viral components, matrix protein or nucleoprotein, are restricted to receiving help almost exclusively from TH clones with the same protein specificity. These observations suggest that, upon B-cell surface immunoglobulin-antigen interaction and uptake of intact virus, B cells specific for viral surface proteins process and present all major structural viral antigens, enabling the B cells to interact with TH clones specific for any virion protein. B cells recognizing internal viral components, which may be accessible to interaction with B-cell immunoglobulin receptors mainly as free proteins, would present only the protein for which they are specific and, thereby, receive help only from the TH clones of the same protein specificity.
TL;DR: All five nucleoside analogs evaluated inhibited the growth of influenza virus types A and B in MDCK cells at a concentration which was well below their cytotoxicity threshold for M DCK cells and, therefore, deserve further exploration for their potential in the treatment of influenzairus type A, B, and C infections.
Abstract: A set of 20 nucleoside analogs were examined for their inhibitory effects on the cytopathogenicity and growth of influenza virus type A, B, and C strains in Madin-Darby canine kidney (MDCK) cells. Among the compounds evaluated, pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and cyclopentenyl cytosine inhibited viral cytopathogenicity at concentrations that were lower than those found cytotoxic for the MDCK cells. No differences were observed in the 50% effective doses (based on inhibition of viral cytopathogenicity) of these five compounds for a number of influenza virus type A (subtypes H1N1 and H3N2), B, and C strains. Pyrazofurin showed the lowest 50% effective dose (0.15 microgram/ml), which was about 20- to 30-fold lower than those of the other four compounds. The selectivity indices of the five compounds, calculated as the ratio of the 50% cytotoxic dose (determined by trypan blue exclusion) to the 50% effective dose, were greater than 100. When the selectivity indices were calculated as the ratios of the 50% inhibitory doses for cellular RNA synthesis to the 50% effective doses, they were greater than 100 for ribavirin, pyrazofurin, and 3-deazaguanine but less than 2 for carbodine and cyclopentenyl cytosine. All five compounds inhibited the growth of influenza virus types A and B in MDCK cells at a concentration which was well below their cytotoxicity threshold for MDCK cells and, therefore, deserve further exploration for their potential in the treatment of influenza virus type A, B, and C infections.
TL;DR: In this paper, the internalization and growth of influenza A NWS virus in macrophagelike P388D1 cells was investigated using fluorescein isothiocyanate-labeled virus and showed that the attachment of normal rabbit serum-exposed virus to neuraminidase (NA)-treated cells was noticeably limited compared with that to untreated cells.
Abstract: We investigated the internalization and growth of influenza A NWS virus in macrophagelike P388D1 cells Flow cytometric analysis using fluorescein isothiocyanate-labeled virus showed that the attachment of normal rabbit serum-exposed virus (NS-V) to neuraminidase (NA)-treated cells was noticeably limited compared with that to untreated cells However, rabbit antiserum-exposed virus (AS-V) could attach equally well to both cells Virus coated with Fab prepared from antiviral immunoglobulin G could not attach These data suggest that the NWS virus can infect P388D1 cells in one of two ways, via viral or via Fc receptors, depending on the presence of antibodies The NS-V could grow in the untreated cells, but not in the NA-treated cells The highest growth of AS-V in the NA-treated cells was observed at an antibody concentration showing 50% plaque reduction titer Growth was exponentially decreased toward the lower and higher dilutions of antibodies By using three different immunoglobulin G subclasses of monoclonal antibodies against hemagglutinin, it was demonstrated that both Fc receptors I and II could take part in this phenomenon The presence of 20 mM NH4Cl inhibited the growth of both AS-V and NS-V, suggesting that the intracellular pathways after internalization via Fc or viral receptors are similar These data indicate that the concentration of antibodies has a critical role on the antibody-mediated growth of influenza virus in macrophages
TL;DR: Despite the low serum response, challenge with a highly pathogenic H7N7 virus revealed complete protection against lethal infection.
Abstract: An influenza virus hemagglutinin gene, H7, has been expressed in a replication-competent Schmidt-Ruppin Rous sarcoma virus-derived vector. This virus, P1/H7, expressed a glycosylated precursor of the H7 protein which was processed to a mature form and transported to the cell surface. The expressed H7 glycoprotein could not be detected in P1/H7 virus particles. A P1/H7 stock which expressed 5 to 10% of the level of H7 observed in influenza virus-infected chicken embryo fibroblasts was used to immunize 1-month-old chickens. This immunization resulted in low or undetectable levels of hemagglutination-inhibiting and neutralizing antibody. Despite the low serum response, challenge with a highly pathogenic H7N7 virus revealed complete protection against lethal infection. Images
Journal Article•
TL;DR: It is concluded that desquamation of the ciliated epithelium of the trachea is not T-cell dependent; and serum antibody can contribute to temporary recovery from infection, but by itself is insufficient for permanent recovery of the nose,trachea or lung.
Abstract: BALB/c normal and nude mice were infected with a non-lethal mouse-passaged A/PC/1/73 (H3N2) influenza virus in order to assess the role of T cells on the course of disease of the nose, trachea and lung. The tracheal epithelium of both mouse strains was desquamated by 3 days after infection. Although normal regeneration began, nude mice never completed that regeneration whereas normal mice had fully regenerated tracheas by Day 14. This failure to complete the recovery was also evident from the continued virus shedding by the nude mouse. In order to assess the role of serum antibody on recovery from infection, ferret, goat or mouse antibody to H3N2 influenza virus was passively administered to nude mice after infection. It resulted in a transient decrease in virus shedding from the nose, trachea and lung, and complete but temporary regeneration of the tracheal epithelium. However, later in the course of the infection, when serum antibody levels were no longer detectable, the tracheal epithelium of these animals redesquamated and large amounts of virus were again shed from nose, trachea and lungs. We conclude that: (i) desquamation of the ciliated epithelium of the trachea is not T-cell dependent; and (ii) serum antibody can contribute to temporary recovery from infection, but by itself is insufficient for permanent recovery of the nose, trachea or lung.
TL;DR: A recombinant vaccinia virus is constructed that expresses surface proteins from two diverse pathogens, influenza A virus haemagglutinin and herpes simplex virus type 1 (HSV-1) glycoprotein D, which could still be effectively immunized with the double recombinant.
Abstract: A global vaccination strategy must take into account production and delivery costs as well as efficacy and safety. A heat-stable, polyvalent vaccine that requires only one inoculation and induces a high level of humoral and cellular immunity against several diseases is therefore desirable. A new approach is to use live microorganisms such as mycobacteria1, enteric bacteria2,3, adenoviruses4, herpes viruses5,6 and poxviruses7 as vaccine vectors. A potential limitation of live polyvalent vaccines, however, is existing immunity within the target population not only to the vector, but to any of the expressed antigens. This could restrict replication of the vector, curtail expression of antigens, and reduce the total immune response to the vaccine. Recently acquired immunity to vaccinia virus can severely limit the efficacy of a live recombinant vaccinia-based vaccine8, so a strategy involving closely spaced inoculations with the same vector expressing different antigens may present difficulties. We have constructed a recombinant vaccinia virus that expresses surface proteins from two diverse pathogens, influenza A virus haemagglutinin and herpes simplex virus type 1 (HSV-1) glycoprotein D. Mice that had recently recovered from infection with either HSV-1 or influenza A virus could still be effectively immunized with the double recombinant.
TL;DR: Swine influenza A (H1N1) viruses were isolated from two people in Switzerland and one in the Netherlands in early 1986 and were closely related to one another and to the A/New Jersey/8/76 strain.
Abstract: Swine influenza A (H1N1) viruses were isolated from two people in Switzerland and one in the Netherlands in early 1986. In haemagglutination-inhibition and neuraminidase-inhibition assays, the three viruses were closely related to one another and to the A/New Jersey/8/76 strain. The Swiss patients showed only mild symptoms, whereas the Dutch patient suffered from severe pneumonia. Two of the patients had been in close contact with diseased pigs. No such contact could be established for the third patient. None of the three individuals was known to suffer from immunodeficiency. No man-to-man transmission of the virus has been detected.
TL;DR: A clear relationship between pre-challenge antibody, measured by single radial haemolysis (SRH), and protection was demonstrated as judged by virus excretion, febrile responses and antibody responses.
Abstract: Thirty-one ponies immunized with inactivated virus vaccine containing A/equine/Miami/63 (H3N8) virus and six seronegative ponies were experimentally challenged with the homologous virus strain. All 6 unvaccinated ponies and 11 out of 31 vaccinated ponies became infected. A clear relationship between pre-challenge antibody, measured by single radial haemolysis (SRH), and protection was demonstrated as judged by virus excretion, febrile responses and antibody responses. Those ponies with SRH antibody levels greater than 74 mm2 were completely protected against challenge infection by the intranasal route.
Journal Article•
TL;DR: The results indicate that antigenic shift variants caused epidemics at various times of the year over this period, whereas drift variants were associated with a regular increase in incidence during the second and fourth calendar quarters.
Abstract: Prospective laboratory surveillance of influenza viruses has been carried out since 1973 in Singapore The results indicate that antigenic shift variants caused epidemics at various times of the year over this period, whereas drift variants were associated with a regular increase in incidence during the second and fourth calendar quarters Outbreaks due to influenza A virus occurred every year and to influenza B virus at intervals of 16-24 months Between outbreaks, viruses belonging to either of the two types could be detected during most months, and certain variants appeared several months before the outbreaks they subsequently caused The factors that contribute to the seasonal pattern are at present unknown
TL;DR: A collection of simian virus 40 plasmid vectors useful for transient or constitutive expression of cDNA or genomic DNA in animal cells is constructed and Membrane-bound as well as secreted forms of the HA glycoprotein lacking the sequence of the C-terminal anchor (HA-) have been obtained.
TL;DR: Festival A virus infection was not found to augment the initiation of NTHi adherence to ciliated respiratory epithelium in this model, and infected tissues demonstrated significantly fewer adherent bacteria than did controls.
TL;DR: The fact that Di-M-PGA2-treatment decreased virus titers in the lungs and did not alter the host immune response, suggested that PGA's therapeutic action was due to suppression of virus replication.
Abstract: We have previously shown that prostaglandins of the A series potently inhibit virus replication in several virus-host systems in vitro. In the present report we have studied the effect of a long-acting synthetic analog of PGA, 16,16-dimethyl-PGA2(Di-M-PGA2), on virus infection in vivo, using as a model Balb/c mice infected with influenza A (PR8) virus. Depending upon the dose of viral inoculum, PR8 virus caused the death of 50 to 100% of the animals in a period of 8-20 days. Di-M-PGA2-treatment significantly increased mouse survival by an average of 40%, independently of the dose of inoculum and the age of the animals. The fact that Di-M-PGA2-treatment decreased virus titers in the lungs and did not alter the host immune response, suggested that PGA's therapeutic action was due to suppression of virus replication. Finally, two anti-inflammatory compounds, which inhibit prostaglandin synthesis, aspirin and indomethacin, were shown not to significantly alter mouse survival in this system.
TL;DR: Both chamber slide and shell vial assays are rapid, sensitive, and specific techniques for the diagnosis of influenza.
Abstract: Murine monoclonal antibodies directed against type-specific antigens of influenza A and B viruses have been shown to be useful diagnostic reagents for the detection of influenza viruses by immunofluorescence testing of nasopharyngeal cells. We have developed fluorescent focus assays utilizing these antibodies in cell culture chamber slides and shell vials for the rapid diagnosis of influenza A and B. Chamber slide assays were compared with virus isolation in 160 specimens from 135 patients with symptoms of influenza. Virus isolation was compared with immunofluorescence testing in 38 of the 160 specimens. Compared with virus isolation, 24-h cell culture chamber slide assays had a sensitivity of 75% and a specificity of 96%. Immunofluorescence testing of nasopharyngeal cells was only 38% sensitive and 91% specific. Shell vial assays were compared with virus isolation for 89 specimens. At 16 to 18 h postinoculation, the shell vial assay was 84% sensitive and 100% specific. We conclude that both chamber slide and shell vial assays are rapid, sensitive, and specific techniques for the diagnosis of influenza.
TL;DR: There is a high sequence homology between both H10 strains supporting the concept that the mink virus has obtained its hemagglutinin from an avian strain.
TL;DR: Gamma‐irradiated virus proved to be more efficient than UV‐inactivated virus in priming for a memory Tc cell response or in boosting memory spleen cells in vitro.
Abstract: Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses
TL;DR: It is concluded that these cold-recombinant virus vaccines are safe and immunogenic in seropositive older high-risk adults and more often induced a nasal wash IgA antibody response than the inactivated virus vaccine.
Abstract: Forty seropositive older adults with chronic diseases were vaccinated intranasally with either influenza A/California/10/78 (H1N1) (CR37) or influenza A/Washington/897/80 (H3N2) (CR48) virus. No clinically significant decrements in pulmonary function occurred postvaccination. Eight (62%) recipients of CR37 virus and 16 (59%) recipients of CR48 virus became infected with vaccine virus, as indicated by a fourfold rise in nasal wash immunoglobulin G (IgG) or IgA antibody titer, a fourfold rise in serum antibody titer, isolation of vaccine virus from nasal washings, or all of these. Within 2 years after cold-recombinant virus vaccination, 29 vaccinees received trivalent inactivated influenza virus vaccine parenterally. After inactivated virus vaccination, 23 (79%) vaccinees developed a fourfold rise in nasal wash or serum antibody titer to H1 antigen and 24 (83%) developed a fourfold rise in nasal wash or serum antibody titer to H3 antigen. Significantly more cold-recombinant virus vaccinees developed a fourfold rise in nasal wash IgA antibody to H1 or H3 hemagglutinin compared with inactivated virus vaccinees (17 [43%] versus 9 [17%], P = 0.01). We conclude that these cold-recombinant virus vaccines are safe and immunogenic in seropositive older high-risk adults and more often induced a nasal wash IgA antibody response than the inactivated virus vaccine.