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The spread and persistence of influenza viruses in normal and cyclophosphamide-treated mice
Abstract:
The persistence and extrapulmonary spread of three strains of influenza virus, the mouse neuro-adapted A/NWS virus, the wild-type strain A/Victoria/75, and a recombinant virus RIT4050, bearing surface antigens derived from A/Victoria/75, were studied in both normal and cyclophosphamide-treated CBA mice following either intranasal or intracerebral inoculation. All three viruses showed increased lethality in mice in the presence of cyclophosphamide but exhibited distinctive patterns of replication and spread. The recombinant virus RIT4050 showed a reduced ability to replicate, persist, and spread in CBA mice compared to either A/NWS or A/Victoria/75 viruses, and in general, the A/NWS virus persisted to a greater extent than the A/Victoria/75 virus in both normal and treated mice. However, in the presence of cyclophosphamide, no extrapulmonary spread of A/NWS virus was observed. The reasons for the differences are discussed.
Insights
Investigating influenza virus strains in mice revealed distinct replication and spread patterns. Cyclophosphamide treatment increased lethality but altered virus behavior, impacting extrapulmonary spread.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Influenza virus strains exhibit varying virulence and host-pathogen interactions.
- Understanding viral persistence and spread is crucial for disease control.
- Immunosuppression can significantly alter the course of viral infections.
Purpose of the Study:
- To compare the persistence and extrapulmonary spread of three distinct influenza virus strains.
- To evaluate the impact of cyclophosphamide-induced immunosuppression on viral pathogenesis.
- To elucidate strain-specific differences in viral replication and dissemination.
Main Methods:
- Intranasal and intracerebral inoculation of CBA mice with A/NWS, A/Victoria/75, and RIT4050 influenza viruses.
- Treatment of mice with cyclophosphamide to induce immunosuppression.
- Monitoring of viral lethality, replication, persistence, and extrapulmonary spread.
Main Results:
- All three influenza virus strains demonstrated increased lethality in cyclophosphamide-treated mice.
- The recombinant virus RIT4050 showed reduced replication, persistence, and spread compared to wild-type strains.
- A/NWS virus generally persisted longer than A/Victoria/75, but its extrapulmonary spread was inhibited by cyclophosphamide.
Conclusions:
- Influenza virus strains possess intrinsic differences in their ability to replicate, persist, and spread.
- Cyclophosphamide treatment modulates influenza virus pathogenesis, affecting lethality and dissemination.
- Strain-specific viral characteristics and host immune status interplay to determine infection outcomes.