Ciarlet M, Estes M K, Barone C, Ramig R F, Conner M E
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Virol. 1998 Mar;72(3):2341-51. doi: 10.1128/JVI.72.3.2341-2351.1998.
The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV x D (G1), RRV x DS-1 (G2), and RRV x ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 10(3) 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction. Also, our results suggest that VP4 may be involved in, but is not exclusively responsible for, host range restriction in the rabbit model. The replication efficiency of rotavirus in rabbits also is not controlled by the product of gene 5 (NSP1) alone, since a reassortant rotavirus with ALA gene 5 and all other genes from SA11 was more severely replication restricted than either parental rotavirus strain.
轮状病毒感染的兔和小鼠模型的主要局限性在于，人类轮状病毒（HRV）毒株在这两种动物中均不能有效复制。确定赋予异源宿主复制能力所需的单个基因，对于理解轮状病毒感染的宿主范围限制至关重要。我们最近报告称，鉴定出四种兔轮状病毒毒株的刺突蛋白VP4的P型为P[14]。为了确定VP4是否参与兔的宿主范围限制，我们评估了用两种P[14] HRV（PA169（G6）和HAL1166（G8））以及其他几种不同P和G型的HRV毒株和动物轮状病毒毒株经口接种无轮状病毒抗体的兔后的感染情况。我们还评估了亲本恒河猴轮状病毒（RRV）（P5B[3]，G3）以及衍生的RRV - HRV重配候选疫苗毒株RRV x D（G1）、RRV x DS - 1（G2）和RRV x ST3（G4）是否能在兔中有效感染。基于病毒排出情况，与同源ALA毒株（P[14]，G3）相比，观察到P[14] HRV毒株以及SA11 Cl3（P[2]，G3）和SA11 4F（P6[1]，G3）动物轮状病毒毒株的复制有限。然而，即使是有限的感染，在接种后28天（DPI）用10³ 50%感染剂量的ALA兔轮状病毒经口攻击兔时，也能提供完全的轮状病毒感染保护。其他HRV毒株不能在兔中有效感染，尽管偶尔有血清转化，但对攻击没有提供显著保护。猿猴RRV在兔中的复制效率与兔ALA轮状病毒一样高，并能提供完全的ALA攻击保护。减毒活RRV重配疫苗毒株在兔中导致无感染、有限感染或有效感染，但所有兔均能完全免受异型ALA攻击。重配毒株在兔中复制效率的改变表明VP7在宿主范围限制中起作用。此外，我们的结果表明VP4可能参与但并非唯一负责兔模型中的宿主范围限制。轮状病毒在兔中的复制效率也不是仅由基因5（NSP1）的产物控制，因为一种具有ALA基因5和来自SA11的所有其他基因的重配轮状病毒的复制限制比任何一种亲本轮状病毒毒株都更严重。
