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Modeling Dysplastic and Functional Lung Alveolar Repair after Influenza Infection
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THE DEMONSTRATION OF LESIONS AND VIRUS IN THE LUNGS OF MICE RECEIVING LARGE INTRA-PERITONEAL INOCULATIONS OF EPIDEMIC
1Laboratories of the International Health Division, The Rockefeller Foundation, New York.
Abstract:
Following the intraperitoneal inoculation of mice with large doses of epidemic influenza virus (50,000 to 1 million intranasal M.L.D.) it can be recovered from the lungs in high concentration, and pulmonary lesions of moderate extent may be observed. The virus reaches its highest titer in the lungs 48 to 72 hours after intraperitoneal injection and may persist for 10 days. Virus may be recovered from the blood in the first 24 hours, but is readily detected in the omentum and peritoneum for 5 to 6 days. Mice which as a result of the intraperitoneal injection of virus show a high concentration of virus in the lungs do not die but become solidly immune to intranasal infection. Moreover, as early as 24 to 48 hours after intraperitoneal inoculation of large amounts of virus the animals may exhibit resistance to infection with fatal doses of virus given intranasally. Influenza virus given intravenously to mice is rapidly removed from the blood but persists in the lungs and induces pulmonary lesions. Virus can also be recovered from the liver for several days. With subcutaneous inoculation of influenza virus, however, the virus does not reach the blood or lungs in detectable amounts although the regional lymph nodes may yield considerable quantities of the agent. A brief consideration is presented of the mechanisms of infection and resistance which may be involved.
Insights
Intraperitoneal inoculation of mice with influenza virus leads to high lung viral concentrations and immunity to intranasal infection. This method establishes resistance to lethal influenza doses within 48 hours.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Influenza virus infection is a significant public health concern.
- Understanding viral dissemination and host immune response is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the distribution and effects of epidemic influenza virus in mice following different inoculation routes.
- To determine the development of immunity and resistance post-infection.
Main Methods:
- Mice were inoculated intraperitoneally, intravenously, or subcutaneously with epidemic influenza virus.
- Viral titers were measured in various organs (lungs, blood, omentum, peritoneum, liver, lymph nodes).
- Pulmonary lesions and survival rates were assessed, alongside resistance to subsequent intranasal challenge.
Main Results:
- Intraperitoneal inoculation resulted in high lung viral titers, moderate pulmonary lesions, and subsequent solid immunity to intranasal infection.
- Virus was detectable in blood early (24 hours) and in the omentum/peritoneum for up to 6 days.
- Intravenous inoculation led to lung persistence and lesions, while subcutaneous inoculation primarily affected regional lymph nodes.
Conclusions:
- Intraperitoneal influenza virus inoculation induces robust pulmonary viral replication and significant protective immunity.
- Different inoculation routes result in distinct patterns of viral distribution and host response.
- Early development of resistance suggests potential therapeutic or prophylactic applications.
