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Herpes simplex virus type 1 mutant strain in1814 establishes a unique, slowly progressing infection in SCID mice
T Valyi-Nagy1, S L Deshmane, B Raengsakulrach
1Wistar Institute, Philadelphia, Pennsylvania 19104.
Abstract:
Ocular infection of immunocompetent (BALB/c) mice with wild-type herpes simplex virus type 1 (HSV-1) 17+ may lead to acute fatal encephalitis; however, in surviving animals, a latent (nonproductive) infection of the nervous system is established. In contrast, 17+ infection invariably kills mice with severe combined immunodeficiency (SCID mice) within 2 weeks. Ocular infection of immunocompetent mice with a mutant HSV-1 strain, in1814, which does not produce a functional alpha-transinducing protein, results in no detectable viral replication in the nervous system during the time corresponding to the acute phase of infection, no mortality, and the establishment of latency. In SCID mice, however, the in1814 virus establishes a unique, slowly progressing infection. In studying the courses of in1814 infection in SCID and BALB/c mice, we found that although intact B- and/or T-lymphocytic functions were required for the control of viral replication in the nervous system, some of the infected neurons of SCID mice seemed to be able to restrict in1814 replication and harbor the virus in a latent state.
Insights
Herpes simplex virus type 1 (HSV-1) latency in the nervous system depends on immune function. Even in immunodeficient mice, some neurons can restrict viral replication, suggesting intrinsic mechanisms for latency.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Herpes simplex virus type 1 (HSV-1) can cause fatal encephalitis in immunocompetent mice, but survivors establish latent infections.
- Severe combined immunodeficiency (SCID) mice are highly susceptible to HSV-1, succumbing rapidly to infection.
- A mutant HSV-1 strain (in1814) lacking alpha-transinducing protein establishes latency in immunocompetent mice without mortality.
Purpose of the Study:
- To investigate the course of in1814 HSV-1 infection in SCID and immunocompetent (BALB/c) mice.
- To determine the role of immune function in controlling viral replication and establishing latency.
- To explore potential neuronal mechanisms for restricting viral replication.
Main Methods:
- Ocular infection of BALB/c and SCID mice with wild-type HSV-1 (17+) and mutant HSV-1 (in1814).
- Monitoring viral replication in the nervous system.
- Assessing mortality and establishing latency.
- Evaluating the impact of B- and T-lymphocytic functions on infection outcome.
Main Results:
- Wild-type HSV-1 (17+) caused fatal encephalitis in SCID mice but latency in surviving immunocompetent mice.
- Mutant HSV-1 (in1814) did not cause mortality or detectable replication in immunocompetent mice, establishing latency.
- in1814 established a unique, slowly progressing infection in SCID mice.
- Intact B- and/or T-lymphocytic functions were necessary for controlling HSV-1 replication in the nervous system.
- Some neurons in SCID mice restricted in1814 replication, harboring the virus in a latent state.
Conclusions:
- Immune function is critical for controlling HSV-1 replication and preventing fatal encephalitis.
- Neuronal cells possess an intrinsic capacity to restrict viral replication and establish latency, even in the absence of a functional immune system.