Promises to keep (Part 2).
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Animal Technicians↗
Biomedical subjects
James D Macy
Publications and source records attributed to James D Macy.
Transmission of enterotropic mouse hepatitis virus from immunocompetent and immunodeficient mice.
Mouse hepatitis virus (MHV) is the most prevalent virus that infects mice, and most MHV strains are enterotropic. Experiments were performed to elucidate the duration of enterotropic MHV-Y shedding by immunocompetent BALB/ c and C57BL/6 mice and immunocompromised B and T cell-deficient mice. Although the use of molecular diagnostics to detect MHV infection is increasing, it is unclear whether the viral RNA detected is always infectious. The ability to detect MHV-Y transmission to sentinel mice exposed directly to infected mice or to soil bedding from infected mice was compared with reverse transcriptase-polymerase chain reaction-based detection of viral RNA in the feces. The BALB/c mice developed subclinical intestinal infection, and transmitted MHV-Y for four weeks. The C57BL/6 mice also developed subclinical intestinal infection, but only transmitted virus for two weeks. The T cell-deficient mice developed severe disseminated disease by two weeks and transmitted virus for four weeks. The B cell-deficient mice developed subclinical intestinal infection and transmitted virus for longer than three months, although virus RNA was not detected in feces late in the infection. Viral RNA detected in the feces of infected mice was almost always infectious. Non-infectious RNA was detected in a few mice for several days after transmission had ceased. In addition, constant exposure of naive mice to infected mice, via the use of serial sentinels, prolonged viral transmission.
Animals↗
Pathogenesis of enterotropic mouse hepatitis virus in immunocompetent and immunodeficient mice.
Mouse hepatitis virus (MHV) is one of the most prevalent viruses infecting laboratory mice. Most natural infections are caused by enterotropic strains. Experiments were done to compare the pathogenesis of enterotropic strain MHV-Y in immunocompetent BALB/c and C57BL/6 mice with that in B and T cell-deficient mice. In situ hybridization was used to identify sites of virus replication, and reverse transcriptase-polymerase chain reaction analysis was used to detect viral RNA in feces and blood. MHV-Y caused acute subclinical infections restricted to the gastrointestinal tract in BALB/c and C57BL/6 mice. Viral RNA was detected in small intestine and associated lymphoid tissues of immunocompetent mice for 1 week and in cecum and colon for 2 weeks. Infected B cell-deficient mice developed chronic subclinical infection also restricted to the gastrointestinal tract. Viral RNA was detected in the small intestine, cecum, colon, and feces for 7 to 8 weeks. In contrast, infected T cell-deficient mice developed multisystemic lethal infection. During the first week, viral RNA was restricted to the gastrointestinal tract. However, by 2 weeks, mice developed peritonitis, and viral RNA was detected in mesentery and visceral peritoneum. Three to four weeks after virus inoculation, T cell-deficient mice became moribund and viral RNA was detected in multiple organ systems. These results suggest that B cells promote clearance of MHV-Y from intestinal mucosa and that T cells are required to prevent dissemination of MHV-Y from the gastrointestinal tract and associated lymphoid tissues.
Animals↗
Pathogenesis of mouse hepatitis virus infection in gamma interferon-deficient mice is modulated by co-infection with Helicobacter hepaticus.
Gamma interferon-deficient (IFN-gamma KO) mice developed a wasting syndrome and were found to be co-infected with Helicobacter sp., and a new isolate of mouse hepatitis virus (MHV) designated MHV-G. The disease was characterized by pleuritis, peritonitis, hepatitis, pneumonia, and meningitis. Initial experiments used a cecal homogenate inoculum from the clinical cases that contained H. hepaticus and MHV-G to reproduce the development of peritonitis and pleuritis in IFN-gamma KO mice. In contrast, immunocompetent mice given the same inoculum developed an acute, self-limiting infection and remained clinically normal. This result confirmed the importance of IFN-gamma in preventing chronic infection and limiting viral dissemination. To understand the role of both agents in the development of peritonitis and pleuritis, IFN-gamma KO mice were infected with either agent or were co-infected with H. hepaticus and MHV-G. Infection with MHV-G induced a multisystemic infection similar to that described in the original cases, with multifocal hepatic necrosis, acute necrotizing and inflammatory lesions of the gastrointestinal tract, and acute peritonitis and pleuritis with adhesions on the serosal surfaces of the viscera. However, mice given H. hepaticus alone had minimal pathologic changes even though the organism was consistently detected in the cecum or feces. Although co-infection with H. hepaticus and MHV-G induced lesions similar to those associated with MHV-G alone, the pathogenesis of the MHV infection was modified. Helicobacter hepaticus appeared to reduce the severity of MHV-induced lesions during the acute phase of infection, and exacerbated hepatitis and meningitis at the later time point. We conclude that infection of IFN-gamma KO mice with MHV-G results in multisystemic infection with peritonitis, pleuritis, and adhesions due to the aberrant immune response in these mice. In addition, co-infection of these mice with H. hepaticus results in alterations in the pathogenesis of MHV-G infection.
Animals↗
Assessment of static isolator cages with automatic watering when used with conventional husbandry techniques as a factor in the transmission of mouse hepatitis virus.
This study evaluated protection against mouse hepatitis virus (MHV) afforded by static filter-top caging when automatic watering was used with conventional husbandry techniques as a labor-saving option. We fitted one side of a double-sided 72-cage rack with valves external to each cage; cages on the other side were fitted with shielded internal valves. More than 50% of the mice were breeding mice, and 30% were genetically altered. One cage of mice on each shelf on both sides of the rack was infected with MHV-A59. Each row of cages also contained one standard cage (no filter top) of uninoculated mice at various distances from the infected cage. At 2, 4, and 6 weeks after infection of the mice in the test cages, uninoculated mice in 22 cages were tested by serology, and at 8 weeks the uninoculated mice in 54 cages were tested by serology and those in 24 cages were tested by polymerase chain reaction (PCR) amplification of fecal samples to assess transmission of infection. At 8 weeks post-infection, mice in one uninoculated cage (which had a filter top and an internal valve and was adjacent to a cage of inoculated mice) was seropositive. Examination of feces by PCR revealed MHV shedding in mice in nine uninoculated cages (three lacking filter tops but with internal valve cages; two with filter tops and internal valve cages and adjacent to non-filter top cages; two non-filter-top cages with external valves; and two filter-top cages with external valves, of which one was adjacent to a non-filter-top cage). Routine husbandry using either automatic water valve system prevented (with one exception) transmission among filter-top cages for at least 6 weeks. The 10 cages where transmission occurred were non-filter-top cages (n = 5) and filter-top cages adjacent to non-filter top, infected, or sentinel cages (n = 5). These results suggest that the use of filter top-caging with automatic watering may limit MHV transmission for 6 weeks, during which immunocompetent mice would be expected to clear the virus. Our findings also suggest that long-term use of automatic watering in static filter-top cages handled using conventional husbandry techniques may not prevent transmission in the vicinity of high virus concentrations or open caging.
Animal Husbandry↗