Related Experiment Video
Updated: Aug 30, 2026
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Confirmed persistent mouse hepatitis virus infection and transmission by mice with a targeted null mutation of tumor
Jennifer K Pullium1, Felix R Homberger, Kimberly A Benjamin
1Division of Animal Resources, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA.
Abstract:
Mouse hepatitis virus (MHV) infection in immunocompetent mice is typically self limiting, and transmission is short lived. With the recent surge in the development of genetically engineered mutant mice with alterations in immune system components, however, MHV clearance may be disrupted. We report confirmed persistent transmission of MHV from tumor necrosis factor (TNF) knockout mice, B6.129S1-Tnftm1Lj (TNF -/-), to nude and immunocompetent sentinel mice over a period of five months. Infection with MHV was confirmed in nude sentinel mice by use of reverse transcriptase-polymerase chain reaction (RT-PCR) detection of viral RNA in ascending colon and feces. The RT-PCR-analyzed specimens recovered from sentinel animals were sequenced, and 92% homology to the N region of the MHV strain S genome was documented. In addition, immunocompetent mice had evidence of seroconversion to MHV infection and RT-PCR-positive fecal and ascending colon specimens after only 24 h of direct contact with the TNF -/- mice. To the authors' knowledge, this is the first reported experimental evidence that MHV transmission can occur for several months, from persistently infected mice to sentinel mice, over a short-term exposure period.
Insights
Tumor necrosis factor (TNF) knockout mice can persistently transmit mouse hepatitis virus (MHV) for at least five months. This persistent MHV transmission was observed in both nude and immunocompetent sentinel mice.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Mouse hepatitis virus (MHV) infection is usually self-limiting in immunocompetent mice.
- Genetically engineered mice with immune system alterations may exhibit disrupted MHV clearance.
Purpose of the Study:
- To investigate persistent transmission of MHV from tumor necrosis factor (TNF) knockout mice.
- To assess MHV transmission dynamics to sentinel mice with varying immune statuses.
Main Methods:
- Utilized reverse transcriptase-polymerase chain reaction (RT-PCR) to detect viral RNA in sentinel mice (ascending colon and feces).
- Sequenced RT-PCR positive specimens to confirm MHV homology (92% to MHV strain S N region).
- Monitored seroconversion and viral shedding in immunocompetent sentinel mice after direct contact.
Main Results:
- Confirmed persistent MHV transmission from TNF knockout mice to nude and immunocompetent sentinel mice over five months.
- Demonstrated rapid MHV infection and transmission (within 24 hours) to immunocompetent sentinels.
- Documented high genetic homology of transmitted MHV to the MHV-S strain.
Conclusions:
- Experimental evidence indicates prolonged MHV transmission from persistently infected TNF knockout mice.
- Short-term exposure can lead to significant transmission to sentinel mice, highlighting potential risks in research settings.
- Immune deficiencies, such as TNF deficiency, can dramatically alter MHV infection and transmission patterns.
