Differential susceptibility of SD and CD rats to a novel rat theilovirus

Abstract

Antibodies to rat theilovirus (RTV) have been detected in rats for many years because of their serologic crossreactivity with strains of Theiler murine encephalomyelitis virus (TMEV) of mice. Little information exists regarding this pathogen, yet it is among the most common viruses detected in serologic surveys of rats used in research. In the study reported here, a novel isolate of RTV, designated RTV1, was cultured from the feces of infected rats. The RTV1 genome contained 8094 nucleotides and had approximately 95% identity with another rat theilovirus, NSG910, and 73% identity with TMEV strains. In addition, the genome size of RTV1 was similar to those of TMEV strains but larger than that reported for NSG910. Oral inoculation of Sprague-Dawley (SD) and CD male rats (n = 10 each group) with RTV1 revealed that SD rats were more susceptible than CD rats to RTV1 infection. At 14 d postinoculation, 100% of SD rats shed virus in the feces, and 70% were positive for RTV serum antibodies. By 56 d postinoculation 30% of SD rats continued to have detectable virus in the feces, and 90% had seroconverted. In contrast, in inoculated CD rats RTV was detected only in the feces at 14 d postinoculation, at which time 40% of CD rats were fecal positive. By 56 d postinoculation only 20% of CD rats had detectable RTV serum antibodies. Our data provide additional sequence information regarding a rat-specific Cardiovirus and indicate that SD rats are more susceptible than CD rats to RTV1 infection.

Figure 1.

Transmission electron micrograph of negatively stained RTV1 particles cultivated in BHK21 cells and purified by cesium chloride gradient centrifugation. Viral particles are approximately 30 nm in diameter with icosahedral symmetry. Bar, 50 nm.

Figure 2.

Alignment of the first 125 nucleotides of the 5′ untranslated regions of TMEV strains GDVII, BeAn (8386), and DA and RTV strains NSG910 and RTV1. Dashes indicate gaps in sequence.

Figure 3.

Percentages of SD and CD rats shedding RTV1 in the feces after oral inoculation with RTV1 (experimental groups) or uninfected BHK21 cell lysates (control groups). The presence of RTV1 in feces was detected by an RTV RT-PCR assay. SD experimental rats, n = 10; CD experimental rats, n = 10; SD control rats, n = 6; and CD control rats, n = 6.

Figure 4.

Percentages of SD and CD rats developing antibodies to RTV1 after oral inoculation with RTV1 (experimental groups) or uninfected BHK21 cell lysates (control groups). Serologic responses were detected by multiplexed fluorescent immunoassays using TMEV strain GDVII virus as antigen. SD experimental rats, n = 10; CD experimental rats, n = 10; SD control rats, n = 6; and CD control rats, n = 6.