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Acute and chronic infection of human lymphoblastoid cell lines with measles virus
Abstract:
Several human continuous lymphoblastoid cell lines (LCL) having T or B characteristics were infected with low and high passage strains of measles virus. All of the cell lines were susceptible to one or the other or to both strains of measles virus with the production of typical syncytial giant cells and released cell-free infectious virus into the supernatant medium. There was no consistent pattern of susceptibility of LCL with either T or B characteristics to infection by measles virus. Viral induced cytolysis of the lymphoblastoid cells in many of the lines was marked, but in the LCL that could be maintained over longer periods of time, a state of chronic, less cytolytic and persistent infection could be established. The infection was characterized by the production of moderate amounts of cell-free infectious virus for up to 4 1/2 months after initial infection with little change in the number of viable cells in culture. Long-term low multiplicity of infection (MOI) experiments demonstrated that the cell-free infectious virus was being produced only by a small number of cells, but the majority of cells in culture contained measles antigen that was in a cell-restricted, noninfectious, or defective form. Electron microscopic examination of the chronically infected cells demonstrated that many of them contained aggregates of hollow tubular intranuclear nucleocapsids whose "stripped" appearance was in marked contrast to the larger granular intracytoplasmic nucleocapsids found during earlier stages of infection. It is theorized that the persistent infection of LCL may serve as a model in understanding the immune mechanisms which permit latent and chronic measles infection in man.
Insights
Measles virus can establish persistent infections in human lymphoblastoid cell lines (LCL), leading to chronic, less cytolytic infections. This persistent measles infection in LCL may model latent infections in humans.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Measles virus (MeV) infection typically causes acute illness.
- Persistent viral infections can evade immune responses and lead to chronic disease.
- Lymphoblastoid cell lines (LCL) are often used to model viral infections in human immune cells.
Purpose of the Study:
- To investigate the susceptibility of human lymphoblastoid cell lines (T and B characteristics) to measles virus infection.
- To characterize the nature of measles virus infection in LCL, including acute and persistent phases.
- To explore the potential of LCL as a model for understanding persistent and latent measles infections in humans.
Main Methods:
- Infection of human T and B lymphoblastoid cell lines (LCL) with low and high passage measles virus strains.
- Monitoring of viral replication, cytolysis, and infectious virus production.
- Long-term culture experiments to establish and characterize persistent infections.
- Electron microscopy to examine viral nucleocapsid morphology in chronically infected cells.
Main Results:
- All tested LCL were susceptible to measles virus, producing syncytia and infectious virus.
- While acute infection caused significant cytolysis, chronic, less cytolytic persistent infections were established in some LCL.
- In persistent infections, only a small fraction of cells produced infectious virus, while most contained cell-restricted measles antigen.
- Electron microscopy revealed distinct intranuclear nucleocapsid structures in chronically infected cells.
Conclusions:
- Human lymphoblastoid cell lines (LCL) can support both acute and persistent measles virus infections.
- Persistent measles infection in LCL involves a complex interplay of infectious and non-infectious viral forms.
- Chronically infected LCL serve as a valuable model for studying immune evasion mechanisms in latent and chronic measles.