GENETIC STUDIES OF INFLUENZA VIRUSES. II. PLAQUE FORMATION BY INFLUENZA VIRUSES IN A CLONE OF A VARIANT HUMAN HETEROPLOID CELL LINE.
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Biomedical subjects
Publications and source records attributed to E D KILBOURNE.
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Schulman, Jerome L. (Cornell University Medical College, New York, N.Y.), and Edwin D. Kilbourne. Induction of partial specific heterotypic immunity in mice by a single infection with influenza A virus. J. Bacteriol. 89:170-174. 1965.-Mice infected 4 weeks previously with influenza A virus were found to be partially immune when challenged with influenza A2 virus. This partial immunity was demonstrated by reduced titers of pulmonary virus, decreased mortality, and less extensive lung lesions. A specific immunological basis for this protection was suggested by the absence of any protection in animals previously infected with influenza B virus when challenged with A2 virus, or in animals previously infected with influenza A virus when challenged with influenza B virus. Parenteral inoculation with inactivated influenza A virus did not induce partial immunity to A2 virus challenge. An accelerated rise of hemagglutinating-inhibiting antibody after A2 virus challenge was demonstrated in animals previously infected with influenza A virus.
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An experimental model has been developed for the reproducible transmission of influenza virus infection from experimentally infected mice to uninfected cage mates. Infector mice transmit influenza virus infection most readily during the period 24 to 48 hours after initiation of their infection. This restricted period of transmission is not due to declining titers of infective virus in the nose, trachea, or lungs of infector mice after 48 hours of infection, since peak titers in these tissues are maintained for another 48 hours. A mouse-adapted strain of A2 virus was found to be more readily transmitted than the mouse-adapted CAM strain of influenza A1 virus, although the CAM strain induced higher pulmonary virus titers and more extensive lung lesions.
Evidence has been presented that with the experimental model described, infected mice vary in their ability to transmit influenza virus infection. This variation is not explained by differences in titers of influenza virus in the nose, throat, trachea, or lungs of good transmitters. Older mice acquire transmitted influenza virus infection more readily than younger mice. Seasonal variations in the incidence of transmitted influenza virus infection occur.
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Mice infected with a non-mouse-adapted Asian strain of influenza A virus suffered an impaired capacity to destroy or remove staphylococci introduced by the respiratory route. This temporary inhibition of local defense mechanisms was of 7 to 10 days' duration. The persistence of staphylococci in the lung following influenza did not appear to alter the nature of the pathologic reaction to influenza virus. The presence of influenza virus infection in the respiratory tract of the mouse did not alter the fate of intravenous staphylococci in the lung or other organs. In 40 to 50 per cent of mice with influenza, purulent bronchopneumonia and infection with Pasteurella and Hemophilus of murine origin were noted. A minority of control animals evidenced such infection. The administration of antimicrobials to which the murine bacteria were susceptible prevented both the appearance of the endogenous infection with Pasteurella or Hemophilus and the purulent sequelae to influenza virus infection. The true picture of uncomplicated bronchopulmonary influenza virus infection was thus separated from the combined virus-bacteria effect otherwise encountered.
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During its serial transfer and cultivation in this laboratory, a human conjunctival cell line (Chang) was observed to change in morphology. Concurrently no change was noted in the susceptibility of the cells to viruses capable of infecting the original cell line. However, it was noted that the derived variant cell line had acquired susceptibility to the induction of cytopathic effects and incomplete virus formation by several strains of influenza viruses. It was then discovered that swine influenza virus and the N-WS strain of influenza A virus could be serially propagated in the derived cell line with production of infective virus. The swine virus required adaptation, but the N-WS strain did not. N-WS and swine influenza viruses multiply with infective virus formation only in the variant conjunctival cell and in no other cell line. Antigenic, cytologic, and virologic evidence is presented that the influenza virus-susceptible variant cell is of human origin and is not a contaminating cell exogenously introduced. Transition of a cell line from complete insusceptibility to susceptibility to virus infection and multiplication has not been described previously.
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