Showing papers on "Influenza A virus published in 1984"
TL;DR: Immunoprecipitation experiments with extracts from variant virus-infected cells prepared in the presence or absence of tunicamycin, which inhibits glycosylation, demonstrate that addition of the new oligosaccharide side chain is required to prevent reaction with the monoclonal antibody.
Abstract: A single amino acid substitution, Asp-63 to Asn-63, was detected in the hemagglutinin of an antigenic variant of the 1968 Hong Kong (H3) influenza virus that was selected by growth of the wild-type virus in the presence of a monoclonal antibody. The mutation generates an oligosaccharide attachment site, Asn-Cys-Thr at residues 63-65, that is glycosylated. Immunoprecipitation experiments with extracts from variant virus-infected cells prepared in the presence or absence of tunicamycin, which inhibits glycosylation, demonstrate that addition of the new oligosaccharide side chain is required to prevent reaction with the monoclonal antibody. Similar experiments with the virus of the 1969 Hong Kong influenza epidemic, A/England/878/69, which also contains a hemagglutinin glycosylated at residue 63, support this conclusion and provide evidence for the epidemiological significance of carbohydrate-mediated modifications of hemagglutinin antigenicity.
440 citations
TL;DR: The results directly implicate CTL as an important antiviral defense mechanism in experimental influenza infection and indicate that both the induction and expression of antiviral effector activity by CTL in vivo is highly specific and therefore favor the concept that CTL express their antiviralEffect in vivo by direct cytolysis of infected cells.
Abstract: Cloned lines of murine cytotoxic T lymphocytes (CTL) directed to type A influenza virus confer complete protection upon adoptive transfer to syngeneic mice lethally infected by influenza virus. The exquisite specificity exhibited by a subtype-specific cloned CTL in culture is reflected in its capacity to eliminate pulmonary virus and mediate recovery only in those mice infected by the virus subtype recognized by this cloned line in vitro. A cross-reactive CTL cloned line protects mice infected by either of two influenza virus subtypes. In mice dually infected with two virus subtypes, the subtype-specific CTL clone only reduces lung virus levels of the recognized virus subtype and cannot prevent these mice from dying. In contrast, adoptive transfer of the cross-reactive CTL clone into mice simultaneously infected with two virus subtypes results in reduction of pulmonary titers of both subtypes and promotes complete recovery. These results directly implicate CTL as an important antiviral defense mechanism in experimental influenza infection. In addition, these results indicate that both the induction and expression of antiviral effector activity by CTL in vivo is highly specific and therefore favor the concept that CTL express their antiviral effect in vivo by direct cytolysis of infected cells.
407 citations
TL;DR: It appears that local secretory IgA plays a causal role in the prevention of cross‐infection by influenza A virus and serum antibody and Tc cells, on the other hand, may be crucial for recovery from such infection.
Abstract: Mice previously infected with an aerosol of A/Rec 31 influenza virus were strongly protected against an aerosol challenge with A/Vic influenza as judged by lung virus titers recovered 2 days after the challenge infection. Such complete homotypic immunity was not achieved by priming with live Rec 31 virus injected i.v. or UV-inactivated Rec 31 virus administered s.c. together with Al(OH)3 and saponin. The reason for the superior protective effect of the natural infection was investigated. The protection induced by respiratory infection with Rec 31 virus was specific for influenza A viruses. It was not correlated with specific serum hemagglutination inhibition antibody titer or cross-reactive cytotoxic T (Tc) cell reactivity. Moreover, the transfer of splenic and lymphoid T cell populations with strong secondary Tc activity did not significantly reduce lung virus titers in recipient mice 3 days after infection. The protection however occurred in parallel with the presence of cross-reactive IgA antibody in the lung washings. It thus appears that local secretory IgA plays a causal role in the prevention of cross-infection by influenza A virus. Serum antibody and Tc cells, on the other hand, may be crucial for recovery from such infection. All mice primed with live Rec 31 virus, administered i.v. or by aerosol and expressing equally high levels of Tc reactivity, survived a lethal challenge with A/PR8 virus. The same challenge, however, killed half of the mice immunized s.c. with inactivated Rec 31 virus which induced only a low level of Tc reactivity.
322 citations
TL;DR: The results show that the influenza A virus gene for NP can play a role in selecting CTL with different specificities and implicate the NP molecule as a candidate for a target structure recognized by both subtype-directed and cross-reactive influenza A-specific cytotoxic T cells.
Abstract: Using genetically typed recombinant influenza A viruses that differ only in their genes for nucleoprotein, we have demonstrated that repeated stimulation in vitro of C57BL/6 spleen cells primed in vivo with E61-13-H17 (H3N2) virus results in the selection of a population of cytotoxic T lymphocytes (CTL) whose recognition of infected target cells maps to the gene for nucleoprotein of the 1968 virus. Influenza A viruses isolated between 1934 and 1979 fall into two groups defined by their ability to sensitize target cells for lysis by these CTL: 1934-1943 form one group (A/PR/8/34 related) and 1946-1979 form the second group (A/HK/8/68 related). These findings complement and extend our previous results with an isolated CTL clone with specificity for the 1934 nucleoprotein (27, 28). It is also shown that the same spleen cells derived from mice primed with E61-13-H17 virus in vivo, but maintained in identical conditions by stimulation with X31 virus (which differs from the former only in the origin of its gene for NP) in vitro, results in the selection of CTL that cross-react on target cells infected with A/PR/8/1934 (H1N1) or A/Aichi/1968 (H3N2). These results show that the influenza A virus gene for NP can play a role in selecting CTL with different specificities and implicate the NP molecule as a candidate for a target structure recognized by both subtype-directed and cross-reactive influenza A-specific cytotoxic T cells.
176 citations
TL;DR: Two mutations in the receptor-binding site of a human hemagglutinin at residues 226 and 228 allowed replication in ducks and resulted in a receptor- binding-site sequence identical to the known avian influenza virus sequences.
Abstract: Avian influenza virus reassortants containing human influenza virus hemagglutinins do not replicate in ducks. Two mutations in the receptor-binding site of a human hemagglutinin at residues 226 and 228 allowed replication in ducks. The mutations resulted in a receptor-binding-site sequence identical to the known avian influenza virus sequences.
156 citations
TL;DR: Viruses possessing N9 NA have two different HA activities and antibody to either HA or NA alone was incapable of inhibiting hemagglutinin by the virus, but antibody to the HA of an H1N9 virus neutralized its infectivity as effectively as it neutralized H 1N1 or H1n2 viruses whose neuraminidases have no HA activity.
145 citations
TL;DR: It was found that the seal viruses were most closely related antigenically and genetically to recent avian virus strains and were readily distinguishable from mammalian viruses, including H7N7 isolate recovered from seals in 1980.
Abstract: Influenza A virus isolates of the H4N5 subtype (which has previously been detected only in birds) were recovered from harbor seals dying of viral pneumonia on the New England coast from June 1982 through March 1983. When these isolates were compared with other mammalian and avian viruses in serological assays and RNA-RNA competitive hybridization, it was found that the seal viruses were most closely related antigenically and genetically to recent avian virus strains and were readily distinguishable from mammalian viruses, including H7N7 isolates recovered from seals in 1980. Unlike any previous isolates from mammals, these recent seal viruses replicate in the intestinal tracts of ducks, a characteristic of avian viruses. The association of avian viruses with influenza outbreaks in seals suggests that transmission of avian viruses to seals is occurring in nature. Potentially, this may be an example of the adaptation of avian viruses to mammals, which would represent an intermediate step in the evolution of new mammalian strains.
143 citations
TL;DR: Experimental data are presented that offer a better understanding of the immunosuppression that accompanies measles virus infection and influenza virus infection of human lymphocytes, which have normal NK cell activity but fail to synthesize IgG or IgM.
Abstract: We present experimental data that offer, in part, a better understanding of the immunosuppression that accompanies measles virus infection. We note that measles virus "silently" infects human lymphocytes and that the infection does not alter lymphocyte survival in vitro. Yet such infected lymphocytes fail to generate natural killer (NK) cell activity or synthesize immunoglobulins (Ig). Thus, the presence of virus within lymphocytes impairs their specific immune functions in the absence of cytolysis. Influenza virus also infects human lymphocytes. In contrast to measles virus infection of resting lymphocytes in which viral antigen is rarely expressed, influenza virus infection of these cells yields viral antigens expressed in the cytoplasm and on the cell surface. Influenza virus-infected lymphocytes have normal NK cell activity but fail to synthesize IgG or IgM.
130 citations
TL;DR: A striking reduction in virus shedding suggests that influenza transmission may be more efficiently interrupted with live than with inactivated virus vaccination.
128 citations
TL;DR: The immunogenicity of several cold-adapted (ca) viruses was compared in CSL mice with that of wild-type parental viruses with similar surface antigens, according to the vaccinating dose required to clear a challenge consisting of 10(4.5) 50% tissue culture infective doses of the wild- type virus.
Abstract: The immunogenicity of several cold-adapted (ca) viruses was compared in CSL mice with that of wild-type parental viruses with similar surface antigens, according to the vaccinating dose required to clear a challenge consisting of 10(4.5) 50% tissue culture infective doses of the wild-type virus. All ca viruses were less immunogenic than their wild-type parental strains by a factor of 10(1.3) to 10(3.4), probably due to the restricted capacity of ca viruses to replicate in the respiratory tracts of mice. However, their immunogenicity was considerably enhanced when two quite small doses were administered 3 weeks apart. The immunogenicity of ca viruses when administered in two doses and wild-type viruses when administered as a single dose varied according to their surface antigens. It was highest for viruses with the H2N2 A/Ann Arbor/6/60 and H3N2 A/Queensland/6/72 surface antigens and lowest for those with H1N1 A/HK/123/77 surface antigens. When two doses consisting of 10(5.0) 50% tissue culture infective doses of A/Ann Arbor/6/60-ca were administered at an interval of 3 weeks, solid immunity was induced against the wild-type A/Ann Arbor/6/60 parental virus, two heterologous H3N2 strains, and an H1N1 strain.
117 citations
TL;DR: Two infections by swine influenza virus, antigenically similar to A/New Jersey/76 (H1N1) virus, were detected during community epidemics with other influenza viruses during virological surveillance of acute respiratory illnesses.
Abstract: Two infections by swine influenza virus, antigenically similar to A/New Jersey/76 (H1N1) virus, were detected during community epidemics with other influenza viruses. The swinelike viruses were obtained during virological surveillance of acute respiratory illnesses, and the clinical symptoms of these two patients were similar to those caused by other respiratory viruses. Both patients reported contact with swine a few days before onset of illness, but in one case it was brief. Serological studies suggested that one patient may have transmitted the virus to his roommate, but spread into the community was not indicated.
TL;DR: The predominant reactivity of influenza A virus- specific CTL differs from that of anti-influenza A antibodies, which are primarily directed towards epitopes on the virus surface glycoproteins, which may be relevant for the role of influenzaA virus-specific CTL in recurrent infections with different influenza A viruses.
Abstract: This paper shows that most murine (C57BL/6) influenza A virus-specific memory cytotoxic T lymphocyte (CTL) clones tested in limiting dilution did not react with the influenza A virus surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). This lysis of syngeneic target cells infected with the influenza A virus strains, Aichi (H3N2), PR8 (H1N1), or recombinant strain X31 (H3N2) indicates that most antigenic epitopes recognized are associated with internal virus determinants. X31 and PR8 share the internal, and X31 and Aichi the external, viral determinants. Extensive CTL cross-reactivity was observed in experiments with target cells infected with virus carrying internal determinants homologous with the priming virus. In contrast, when the internal viral determinants differed between the priming virus and the virus used to infect the target cells, and although HA and NA were homologous, we found almost complete CTL-specificity for the priming virus. Thus, the predominant reactivity of influenza A virus-specific CTL differs from that of anti-influenza A antibodies, which are primarily directed towards epitopes on the virus surface glycoproteins. This finding may be relevant for the role of influenza A virus-specific CTL in recurrent infections with different influenza A viruses.
TL;DR: Despite the continued presence of high levels of functional host cell mRNAs, host cell protein synthesis was effectively shut off by about 3 h postinfection in both chicken embryo fibroblasts and HeLa cells, consistent with the establishment of an influenza virus-specific translational system that selectively translates viral and not host mRN as.
Abstract: Influenza virus infection has adverse effects on the metabolism of two representative RNA polymerase II transcripts in chicken embryo fibroblasts, those coding for beta-actin and for avian leukosis virus (ALV) proteins. Proviral ALV DNA was integrated into host cell DNA by prior infection with ALV. Within 1 h after influenza virus infection, the rate of transcription of beta-actin and ALV sequences decreased 40 to 60%, as determined by labeling the cells for 5 min with [3H]uridine and by in vitro, runoff assays with isolated nuclei. The transcripts that continued to be synthesized did not appear in the cytoplasm as mature mRNAs, and the kinetics of labeling of these transcripts strongly suggest that they were degraded in the nucleus. By S1 endonuclease assay, it was confirmed that nuclear ALV transcripts disappeared very early after infection, already decreasing ca. 80% by 1 h postinfection. A plausible explanation for this nuclear degradation is that the viral cap-dependent endonuclease in the nucleus cleaves the 5' ends of new polymerase II transcripts, rendering the resulting decapped RNAs susceptible to hydrolysis by cellular nucleases. In contrast to the nuclear transcripts, cytoplasmic beta-actin and ALV mRNAs, which are synthesized before infection, were more stable and did not decrease in amount until after 3 h postinfection. Similar stability of cytoplasmic host cell mRNAs was observed in infected HeLa cells, in which the levels of actin mRNA and two HeLa cell mRNAs (pHe 7 and pHe 28) remained at undiminished levels for 3 h of infection and decreased only slightly by 4.5 h postinfection. The cytoplasmic actin and pHe 7 mRNAs isolated from infected HeLa cells were shown to be translated in reticulocyte extracts in vitro, indicating that host mRNAs were not inactivated by a virus-induced modification. Despite the continued presence of high levels of functional host cell mRNAs, host cell protein synthesis was effectively shut off by about 3 h postinfection in both chicken embryo fibroblasts and HeLa cells. These results are consistent with the establishment of an influenza virus-specific translational system that selectively translates viral and not host mRNAs.
TL;DR: The complete nucleotide sequence of the hemagglutinin (HA) gene of influenza B virus B/Oregon/5/80 is reported and amino acid substitutions in the HA1 polypeptide responsible for the antigenic alterations in laboratory-selected antigenic variants of this virus are identified.
Abstract: We report here the complete nucleotide sequence of the hemagglutinin (HA) gene of influenza B virus B/Oregon/5/80 and, through comparative sequence analysis, identify amino acid substitutions in the HA1 polypeptide responsible for the antigenic alterations in laboratory-selected antigenic variants of this virus. The complete nucleotide sequence of the B/Oregon/5/80 HA gene was established by a combination of chemical sequencing of a full-length cDNA clone and dideoxy sequencing of the virion RNA. The nucleotide sequence is very similar to previously reported influenza B virus HA gene sequences and differs at only nine nucleotide positions from the B/Singapore/222/79 HA gene (Verhoeyen et al., Nucleic Acids Res. 11:4703-4712, 1983). The nucleotide sequences of the HA1 portions of the HA genes of 18 laboratory-selected antigenic variants were determined by the dideoxy method. Comparison of the deduced amino acid sequences of the parental and variant HA1 polypeptides revealed 16 different amino acid substitutions at nine positions. All amino acid substitutions resulted from single-point mutations, and no double mutants were detected, demonstrating that as in the influenza A viruses, single amino acid substitutions are sufficient to alter the antigenicity of the HA molecule. Many of the amino acid substitutions in the variants occurred at positions also observed to change in natural drift strains. The substitutions appear to identify at least two immunodominant regions which correspond to proposed antigenic sites A and B on the influenza A virus H3 HA.
Journal Article•
TL;DR: The study revealed that allergic sensitization could be elicited only during the acute stage of the infection, but not in the convalescent stage, and concluded that the inflammation of respiratory mucous membrane might allow inhaled antigens to penetrate the barrier, resulting in reaginic antibody production that has the capacity to serve as an allergic response.
Abstract: An IgE antibody specific to ovalbumin was produced when C3H mice were first infected with influenza A virus before challenge with the aerosolized antigen. No antibody could be detected in those animals without preceding viral infection. Antigen inhalation immediately after virus infection could not induce the IgE antibody. A time lag of at least 2 days was required to sensitize the infected mice with inhaled antigen. The study revealed that allergic sensitization could be elicited only during the acute stage of the infection, but not in the convalescent stage. We concluded therefore that the inflammation of respiratory mucous membrane might allow inhaled antigens to penetrate the barrier, resulting in reaginic antibody production that has the capacity to serve as an allergic response.
TL;DR: Treating patients with ribavirin aerosol treatment of influenza A(H1N1) virus infection among college students had a significantly shorter duration of fever than control patients and there was a trend of more rapid recovery in treated patients.
Abstract: In a randomized, controlled study of ribavirin aerosol treatment of influenza A(H1N1) virus infection among college students, treated patients had a significantly shorter duration of fever than control patients. There was a trend of more rapid recovery in treated patients. Virus shedding was similar in treated and control patients, declining gradually from a 50% tissue culture infective dose of 3.5 log10 per ml at admission to 1.8 log10 per ml at 53 h after admission. There was no local or systemic intolerance and no hematological or biochemical abnormalities associated with ribavirin treatment.
TL;DR: Clinical and laboratory data of 12 previously healthy infants under 3 months of age hospitalized for suspected sepsis and subsequently diagnosed as suffering from influenza A viral infection were obtained prospectively during two epidemics of influenza A/Bangkok/H3N2 epidemics.
TL;DR: This is the first confirmation of transplacental influenza infection in a gravid woman in association with fever, chills, and uterine tenderness and contractions together with maternal and fetal tachycardia.
TL;DR: Hemagglutination inhibition inhibition antibody (titer, greater than or equal to 1:32) to H3N2 was significantly associated with protection from illness and infection with influenza A/H3n2.
Abstract: One hundred three young children were inoculated intranasally with either influenza A/California/10/78 cold-recombinant vaccine (10(6.7) 50% tissue culture infective doses [TCID50] per child), CR-37 (H1N1), or influenza A/Washington/897/80 cold-recombinant vaccine (10(6.5) TCID50 per child), CR-48 (H3N2). The vaccine was well tolerated. Of the 51 children vaccinated with CR-37 (H1N1), 45 were initially seronegative for this virus; 33 of the 45 became infected with the vaccine virus, as indicated by a fourfold rise in antibody titer or by shedding of vaccine virus. Of the 52 children vaccinated with CR-48 (H3N2), six were initially seronegative and all were infected; 46 were initially seropositive and 25 of these children developed fourfold rises in antibody titer. An outbreak of influenza A (H3N2 type predominated) occurred in Huntington one to three months after the children were vaccinated. Significantly fewer febrile illnesses occurred in the CR-48 (H3N2) vaccine group than among the CR-37 (H1N1) vaccine group. Hemagglutination inhibition antibody (titer, greater than or equal to 1:32) to H3N2 was significantly associated with protection from illness and infection with influenza A/H3N2.
TL;DR: Human interferon-alpha 2 interacted additively or synergistically with rimantadine hydrochloride or ribavirin in reducing the yield of clinical isolates of either H3N2 or H1N1 subtype influenza A viruses and inhibited the replication of an influenza B virus to a greater extent than either single agent.
Abstract: Recombinant DNA-produced human interferon-alpha 2 inhibited the replication of influenza A and B viruses in primary rhesus monkey kidney cells (RMK). Human interferon-alpha 2 interacted additively or synergistically with rimantadine hydrochloride or ribavirin in reducing the yield of clinical isolates of either H3N2 or H1N1 subtype influenza A viruses. The combination of human interferon-alpha 2 and ribavirin also inhibited the replication of an influenza B virus to a greater extent than either single agent. In addition to drug concentration, the virus inoculum and duration of culture were important variables in determining the degree of inhibition. Single drugs or combinations did not significantly inhibit the growth of uninfected RMK cells, which indicated that the observed interactions with respect to antiviral activity were not due to cell cytotoxicity.
TL;DR: It is suggested that Verapamil and chlorpromazine inhibit influenza virus replication by interfering with calmodulin-dependent intracellular activities necessary for late synthetic steps or virus assembly steps and that calcium channel blockers provide a new probe for investigating influenzairus replication.
Abstract: Calcium channel blockers reduce Ca++ flux through membrane channels and may inhibit intracellular Ca++-dependent synthetic and regulatory activities by binding to calmodulin. We have found that Verapamil, a calcium channel blocker, inhibits influenza virus replication in Madin-Darby canine kidney cells and in murine pulmonary macrophages and that this antiviral effect occurs with drug addition late in the replication cycle. Chlorpromazine, a drug which binds to calmodulin, also inhibited influenza virus replication in these tissue culture systems. We suggest that Verapamil and chlorpromazine inhibit influenza virus replication by interfering with calmodulin-dependent intracellular activities necessary for late synthetic steps or virus assembly steps and that calcium channel blockers provide a new probe for investigating influenza virus replication.
TL;DR: It is demonstrated that immune complexes of detectable size are induced by influenza virus infection during the interface between antigen excess and antibody excess conditions and the suppressive effects of immune complexes on alveolar macrophages may, in part, explain the phagocytic dysfunction that occurs 7 to 10 days after influenza virus pneumonia.
Abstract: Immune complexes in the lungs are capable of inducing adverse responses. Herein we have detailed the formation of immune complexes in the lungs of influenza virus-infected mice and examined their effect on alveolar macrophage defenses. On days 3, 7, 10, 15, and 30 after aerosol infection with influenza A/PR8/34 virus, the acellular pulmonary lavage fluid was tested for viral antigen, specific viral antibody, and immune complexes by immunoassays. Whereas peak viral antigen (day 3) diminished to undetectable levels by day 10, specific viral antibody remained at a low concentration until day 10, after which it rapidly increased. Immune complex concentrations increased through day 7, peaked at day 10, and gradually returned to the control level by day 30. These data demonstrate that immune complexes of detectable size are induced by influenza virus infection during the interface between antigen excess and antibody excess conditions. Since alveolar macrophages are the pivotal phagocytic defense cells in the lung, the ability of normal alveolar macrophages to ingest opsonized erythrocytes was quantitated in the presence of immune complexes from lavage fluid. Immune complexes from day 10 virus-infected lungs caused a dose-dependent suppression of antibody-mediated phagocytosis to 30% of control values. In contrast, although these immune complexes also markedly decreased the phagocytosis of antibody-coated yeast cells, they did not significantly impair the antibody-independent ingestion of unopsonized yeast cells by macrophages. the suppressive effects of immune complexes on alveolar macrophages may, in part, explain the phagocytic dysfunction that occurs 7 to 10 days after influenza virus pneumonia.
TL;DR: Seronegative children inoculated intranasally with influenza A/California/10/78 (H1N1) cold-recombinant vaccine (CR-37) conferred significant protection from challenge with a high dose of CR-37.
Abstract: Forty-seven seronegative children were inoculated intranasally with influenza A/California/10/78 (H1N1) cold-recombinant vaccine (CR-37). Doses ranged from 10(3.2) to 10(7.2) TCID50 per child. The dose necessary to infect 50% of children (one HID50 ) was approximately 10(3.5) TCID50. Only two of eight children given 10(3.2) TCID50 became infected, and neither shed virus. The majority of children who were given 10(4.2), 10(5.2), 10(6.2), or 10(7.2) TCID50 of CR-37 became infected. Twenty-four of 39 children given greater than one HID50 of CR-37 shed vaccine virus. Overall, 31 of 39 became infected, as indicated by shedding of virus or antibody response or both. Although virus was shed for up to 12 days postinoculation, shedding of revertant virus was not detected. Six months after primary vaccination 26 children were challenged intranasally with 10(6.2) TCID50 of CR-37. Of 21 children previously infected with CR-37, only eight had further antibody increase, and none shed vaccine virus. In contrast, five of five (P less than .05) children not infected with CR-37 at the time of initial inoculation were infected with the challenge inoculum (as indicated by a fourfold rise in antibody titer) and three of five children shed vaccine virus. Previous infection with CR-37 conferred significant protection from challenge with a high dose of CR-37.
TL;DR: Antibody determinations against H3N2 and H1N1 type A influenza viruses were carried out on paired sera obtained from volunteers taking part in influenza virus vaccine studies, using both the haemagglutination-inhibition (HI) and single radial haemolysis (SRH) test.
Abstract: Antibody determinations against H3N2 and H1N1 type A influenza viruses were carried out on paired sera obtained from volunteers taking part in influenza virus vaccine studies, using both the haemagglutination-inhibition (HI) and single radial haemolysis (SRH) test. Good correlation between the HI and SRH test was found for both H3N2 and H1N1 antibody and the zone area increases corresponding to significant SRH antibody rises determined for both virus strains. In both H3N2 and H1N1 vaccine studies, intranasal infection of the volunteers with live attenuated viruses was involved and by the measurement of HI and SRH antibodies prior to and following infection, levels of antibody equating with protection against the infecting viruses could be estimated. For the HI test the antibody titres associated with 50% protection were 42 for H1N1, and 44 for H3N2 viruses; for the SRH test, 50% protection was associated with zone areas of 20.0-25.0 mm2 for both H1N1 and H3N2 viruses.
TL;DR: A representative T-cell clone has been used in combination with a set of genetically typed recombinant viruses, to show that the A/PR/8/34 nucleoprotein can be responsible for cytotoxic T-lymphocyte recognition of infected target cells.
TL;DR: A specific inhibitory mechanism for influenza virus translation was induced by IFN-alpha + beta in macrophages bearing the resistance gene Mx, which resulted in a twofold reduction in the accumulation of primary transcripts and a marked shut-off of influenza virus polypeptide synthesis.
Abstract: In mice, the combined action of alpha and beta interferons (IFNs) against influenza viruses is modulated by the host gene Mx. High concentrations of IFN fail to prevent efficiently the replication of influenza A virus in cultured macrophages lacking the gene Mx, whereas cultured macrophages carrying Mx develop strong antiviral activity even at low concentrations of IFN. Several steps in the replication cycle of influenza virus were compared in Mx/Mx and +/+ mouse macrophages treated with IFN-alpha + beta. Uncoating was not affected. A twofold reduction in the accumulation of primary transcripts was observed in IFN-treated macrophages at the highest concentration of IFN regardless of the genetic constitution of the host cell. No evidence was obtained for inhibition of influenza virus translation in macrophages which lacked Mx when treated with IFN-alpha + beta. In contrast, a marked shut-off of influenza virus polypeptide synthesis occurred in Mx-bearing macrophages treated with these IFNs, although the primary transcripts were active in directing the synthesis of viral polypeptides in a cell-free system. We concluded that a specific inhibitory mechanism for influenza virus translation was induced by IFN-alpha + beta in macrophages bearing the resistance gene Mx.
TL;DR: Analysis of the genome composition of the recombinants obtained by recombination of the cold-adapted donor with wild-type influenza virus strains A/Leningrad/322/79 (H1N1) and A/Bangkok/1/79(H3N2) showed that recombinant 47/25/1(H1n1)
Abstract: A previously described cold-adapted attenuated virus, A/Leningrad/134/17/57 (H2N2), was further modified by 30 additional passages in chicken embryos at 25 degrees C. This virus had a distinct temperature-sensitive (ts) phenotype, grew well in chicken embryos at 25 degrees C, and failed to recombine with reference ts mutants of fowl plague virus containing ts lesions in five genes coding for non-glycosylated proteins (genes 1, 2, 5, 7, and 8). Recombination of A/Leningrad/134/47/57 with wild-type influenza virus strains A/Leningrad/322/79 (H1N1) and A/Bangkok/1/79(H3N2) yielded ts recombinants 47/25/1(H1N1) and 47/7/2 (H3N2). These recombinants inherited their ts phenotype and ability to reproduce in chicken embryos at 25 degrees C from the cold-adapted parent. Analysis of the genome composition of the recombinants obtained by recombination of the cold-adapted donor with wild-type influenza virus strains A/Leningrad/322/79(H1N1) and A/Bangkok/1/79(H3N2) showed that recombinants 47/25/1(H1N1) and 47/7/2 (H3N2) inherited five and six genes, respectively, from the cold-adapted parent, and hemagglutinin and neuraminidase genes from the wild-type strains.
TL;DR: Although very little infectious virus was produced when cells were infected with these late pi viruses, cytopathology frequently occurred and an unusual pattern of viral protein synthesis was observed.
TL;DR: The result of this analysis supports the idea of a common lineage of human influenza A viruses isolated over a 43-year period.
Abstract: The influenza virus host range mutant CR43-3, derived by recombination from the A/Alaska/6/77 and the cold-adapted and temperature-sensitive A/Ann Arbor/6/60 viruses, has previously been shown to possess a defect in the NS gene. To characterize this defect, nucleotide sequence data were obtained from cloned cDNAs. The CR43-3 NS gene was found to be 854 nucleotides long and to derive from the NS gene of the A/Alaska/6/77 parent virus by an internal deletion of 36 nucleotides. Direct sequencing of RNA 8 of CR43-3 virus confirmed that the deletion in the NS1-coding region was not an artifact that was generated during the cloning procedure. Protein analysis indicated that the NS1 protein of CR43-3 virus was synthesized in equal amounts in the restrictive (MDCK) cells as well as in the permissive (PCK) host cells. Also, indirect immunofluorescence studies of virus-infected cells showed that the NS1 protein of CR43-3 virus, like that of the parent viruses, accumulates in the nuclei of both cell systems. Although no differences in synthesis or localization of the NS1 protein could be detected, a consistent reduction in M1 protein was noted in CR43-3 virus-infected, nonpermissive cells as compared with that of the permissive host. Since analysis of the CR43-3 virus required us to obtain the NS nucleotide sequence of the 1977 isolate A/Alaska/6/77, we were able to compare this sequence with those of corresponding genes of earlier strains. The result of this analysis supports the idea of a common lineage of human influenza A viruses isolated over a 43-year period.
TL;DR: The results suggest that the influenza-specific CTL response may be a sensitive indicator of immunologic defects in asymptomatic homosexuals and whether healthy homosexual men are immunologically impaired.
Abstract: To determine whether healthy homosexual men are immunologically impaired, peripheral blood leukocytes (PBL) from 20 male homosexuals were compared prospectively with PBL from 14 age-matched male heterosexual donors with respect to: (a) the capacity of their PBL to generate functional T cell immune responses in vitro; and (b) the content of total T cells and T cell subsets in their peripheral blood. The homosexual donors studied indicated moderate sexual life styles in that all but one of the donors had less than five current sexual partners. The percentages of OKT3+, OKT4+, and OKT8+ T cells were similar to those of heterosexual controls. T cell function was assessed by measuring cytotoxic T cell responses to influenza virus and to allogeneic cells. Approximately one-third of the homosexual donors consistently exhibited weak cytotoxic T lymphocyte (CTL) responses to influenza virus, whereas all of the heterosexual donors generated strong CTL responses to influenza. There was no correlation between the strength of CTL responsiveness to influenza virus and the strength of CTL responses to allogeneic cells. These results suggest that the influenza-specific CTL response may be a sensitive indicator of immunologic defects in asymptomatic homosexuals. If acquired immune deficiency syndrome results from an infectious agent, it remains to be seen if such immunosuppression predisposes to the infection, or if it reflects early consequences of infection.