Pravin N. Bhatt

Evidence that NK cells and interferon are required for genetic resistance to lethal infection with ectromelia virus

SummaryC 57 BL/6 mice developed resistance to lethal intravenous challenge with virulent (Moscow strain) ectromelia virus between 2 and 3 weeks of age. The fraction of C 57 BL/6 mice in which virus was detected in spleen was significantly lower than for DBA/2 mice by day 3. Thereafter, C 57 BL/6 mice had significantly reduced virus titers in spleen compared with those of DBA/2 mice. Resistance was abrogated by treatment with anti-asialo GM1 gammaglobulin, which blocks NK cell activity, or with anti-interferon (IFN) α, β. C 57 BL/6 mice carrying the bg/bg mutation, associated with a deficiency of NK cells, were highly susceptible to lethal infection as were athymic mice derived from a resistant genetic background. Virus titers in spleens of C 57 BL/6 mice treated with anti-asialo GM1 or anti-IFN α, β were significantly higher 4 days after virus challenge than were titers in C 57 BL/6 mice treated with normal rabbit serum. The results strongly suggest that genetic resistance to lethal ectromelia virus infection requires non-specific host defenses such as NK cells and IFN α, β that are activated during the first 3 to 4 days of infection.

Pathogenesis of Sialodacryoadenitis in Gnotobiotic Rats

The pathogenesis of sialodacryoadenitis was studied in gnotobiotic CD rats inoculated intranasally with the causal virus. Virus replication was detected sequentially in the nasopharynx, tracheobronchial tree, cervical lymph nodes, submaxillary and parotid salivary glands, exorbital gland, and Harderian gland. Acute rhinitis appeared within 2 days after inoculation, and salivary glands had lesions in 4 days. Early changes in salivary and exorbital glands were characterized by necrosis of ductal epithelium, which rapidly progressed to widespread acinar necrosis, marked inflammation, edema and total effacement of glandular architecture. Harderian glands also had massive necrosis of tubuloalveolar units. Repair in all glands was characterized by marked squamous metaplasia of ducts. Neutralizing and complement-fixing antibodies were detected in 7 days, and there was a concomitant decrease in tissue-virus titers. There was no detectable evidence for hematogenous spread of virus or for retrograde infection by way of major salivary ducts.

Characterization of the Virus of Sialodacryoadenitis of Rats: A Member of the Coronavirus Group

Abstract The virus that causes sialodacryoadenitis in rats has been isolated in mice and in primary cultures of rat-kidney cells and has been characterized as a heat-labile RNA virus that is sensitive to lipid solvents and is relatively stable at pH 3.0. This virus is antigenically related to the virus of hepatitis in mice and to coronavirus of rats. The range of hosts of this agent appears to be narrow. On the basis of available biologic characteristics, it has been placed in the coronavirus group.

Naturally occurring lethal parvovirus infection of juvenile and young-adult rats.

A lethal disease characterized by hemorrhage and necrosis of the brain, testes, and epididymides developed in young adult rats housed in specific pathogen free quarters. Morphological, virological, and serological investigations of the outbreak indicated that the probable causative agent was rat virus (Kilham), a common parvovirus of rats that usually Induces persistent, asymptomatic infection in adult rats.

The pathogenesis of rat virus infection in infant and juvenile rats after oronasal inoculation

SummaryThe pathogenesis of rat virus (RV) infection was studied in random-bred Sprague-Dawley rats after oronasal inoculation of a recent RV isolate designated RV-Yale (RV-Y). RV-Y was pathogenic for rats inoculated as infants (2 days) whereas rats inoculated as juveniles (4 weeks) had asymptomatic infection and no lesions. Rats inoculated as infants developed pantropic infection accompanied by hepatic necrosis, granuloprival cerebellar hypoplasia and hemorrhagic encephalopathy. Virological and serological studies showed that virus could persist in inoculated rats for at least 35 days and for at least 28 days after seroconversion was first detected. Immuno-histochemical results indicated that RV-Y infects tissues conducive to virus excretion including kidney and lung. RV-Y also was found in genital tissues of some rats. Athymic juvenile rats inoculated intraperitoneally with RV-Y had a poor humoral immune response and harbored infectious virus for at least 3 weeks, whereas infection in euthymic control rats was detected for 1 week. These studies indicate that RV-Y can persists in the presence of humoral immunity and suggest that transmission of infection could occur for a substantial period after seroconversion. They also suggest that immunodeficient rats have increased susceptibility to persistent infection.

Persistence of rat virus in seropositive rats as detected by explant culture

SummaryRat virus (RV) was detected by explant culture for up to 14 weeks in rats inoculated as infants and for up to 7 weeks in rats inoculated as juveniles, although both groups were seropositve by 3 weeks post-inoculation.

Stabilized Suspensions of Monkey Kidney Cells Suitable for Intercontinental Shipment.

Summary A method for stabilizing cell suspensions prepared by trypsinization of monkey kidneys is described. Such suspensions prepared in India and shipped to the United States were found to produce cultures useful for the propagation of poliovirus and the production of complement-fixing antigens.

Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus V. Genetics of resistance to the Moscow strain

SummaryThe genetics of resistance to the Moscow strain of ectromelia virus was examined in crosses derived from resistant C57BL/6 (B6) and susceptible DBA/2 (D2) mice. Infection with 101 to 105 PFU of virus resulted in mortalities of 90 to 100% of D2, 0% of B6 and 0 to 3% of (B6 × D2) F1 mice by day 21. Among F1 × D2 backcross progeny, 49% of male and 18% of female mice died. Reciprocal backcrossing did not alter male or female mortality rates. These data are consistent with a single autosomal dominant gene controlling resistance to ectromelia in male mice and at least one additional dominant sex-limited gene controlling resistance in female mice. Fewer male F2 mice died than were predicted based on single-locus control and 32% of recombinant inbred (RI) strains derived from B6 and D2 progenitors expressed non-parental phenotypes. Therefore, additional resistance genes, not expressed in backcross mice, were apparently expressed in F2 mice and RI strains.

Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. IV. Studies with the Moscow strain

SummaryThe pathogenesis and transmission of infection with the Moscow strain of ectromelia virus were studied in inbred mice. BALB/cAnNcr had high morbidity and mortality and C57BL/6Ncr (B6) mice had high morbidity and low mortality. Virus was detected in B6 mice for 2 weeks after subcutaneous (s.c.) inoculation and infected mice developed lesions compatible with acute mousepox. B6 inoculated by footpad transmitted infection to cagemates for up to five weeks and soiled cages that had housed infected mice were infectious for three weeks. S.c.-inoculated B6 mice also transmitted by contact for 2 weeks. Transmission was attributed to oronasal excretion of virus. Airborne transmission of infection between adjacent cages occurred at a low rate. Ectromelia virus-free progeny were derived from previously infected dams. These studies indicate that the highly virulent and infectious Moscow strain of ectromelia virus caused self-limiting infection in inbred mice and that direct contact is the most efficient means of transmission. These findings support the concept that mousepox can be contained by husbandry practices that minimize or eliminate the spread of infection by direct contact or fomites.

Sendai viral pneumonia in aged BALB/c mice

Sendai virus (SV) infection in aged BALB/c mice was evaluated as a natural model for age-associated susceptibility to viral pneumonia. Young (2 month-old) and aged (22-24 month-old) BALB/c mice were inoculated intranasally with 100 median pneumonia doses (PD50) of SV and examined at 6, 10, and 20 days by virus titration, immunohistochemistry, histopathology, and serology. The aged mice had significantly higher virus titers in lung, prolonged infection, delayed development, and resolution of pneumonia and significantly lower serum antibody titers. In a second experiment, the responses of young mice were compared to intermediate-aged mice (11-13 and 17-18 months old). The intermediate-aged mice had some characteristics of young mice and others of aged mice. The results indicate that SV infection can be used to study aging-associated susceptibility to a pneumotropic virus in a natural host, and that susceptibility of mice to viral pneumonia increases gradually during aging.