Rotavirus genome segment 7 (NSP3) is a determinant of extraintestinal spread in the neonatal mouse

被引:51
作者
Mossel, EC [1 ]
Ramig, RF [1 ]
机构
[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
关键词
D O I
10.1128/JVI.76.13.6502-6509.2002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We used the neonatal mouse model of rotavirus infection to study extraintestinal spread following oral inoculation. Five-day-old pups were inoculated with either SA11-C3, SA11-C14, SA11-4F, RRV, or B223. By using virus detection in the liver as a proxy determination for extraintestinal spread, rotavirus strains capable of extraintestinal spread at high frequency (rhesus rotavirus [RRV]) and very low frequency (SA11-C14) were identified. Both strains productively infected the gastrointestinal tract. Oral inoculation of mice with RRV/SA11-C14 reassortants and determination of virus titers in the gut and liver revealed that the extraintestinal spread phenotype segregated with RRV genome segment 7 to a high level of significance (P = 10(-3)). RRV segment 7 also segregated with the growth of virus in the gut (P = 10(-5)). Although infection of the gut was clearly required for tropism to the liver, there was no correlation between virus titers in the gut and detection of virus in the liver. Five days after intraperitoneal administration to bypass the gut barrier to virus spread, RRV and SA11-C14 both were recovered in the liver. However, only RRV was found in the liver following subcutaneous inoculation, suggesting that this peripheral site presented a similar barrier to virus spread as the gut. Sequence analysis of segment 7 from parental RRV and SA11-C14 and selected reassortants showed that (i) amino acid differences were distributed throughout the coding sequences and not concentrated in any particular functional motif and (ii) parental sequence was preserved in reassortants. These data support the hypothesis that NSP3, coded for by genome segment 7, plays a significant role in viral growth in the gut and spread to peripheral sites. The mechanism of NSP3-mediated tropism is under investigation.
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页码:6502 / 6509
页数:8
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