Several members of the virus family Togaviridae cause acute and persistent arthritis and/or arthralgia in humans. A small animal model will be used to study Togavirus tropism for bone/joint tissue.
The specific aims of this study are: 1) Identify cellular targets of acute S.A.AR86 replication within bone/joint tissue. 2) Characterize persistent S.A.AR86 infection within the bone marrow at the molecular level. 3) Determine whether acute and/or persistent replication is a common trait of arthritis/arthralgia-associated Togaviruses. A S.A.AR86 infectious cDNA clone, as well as replication competent viral vectors expressing green fluorescent protein will facilitate identification of virus infected cells. Sequence analysis of persistent virus genomes will be performed to determine if specific mutations contribute to persistence within bone/joint tissue. Other arthritis/arthralgia- associated Togaviruses, including Ross River virus and rubella virus will also be evaluated for the ability to acutely or persistently infect bone/joint tissue within this model. Basic studies within this mouse model may provide insight into mechanisms underlying virus-induced arthritis/arthralgia in humans.
| Heise, Mark T; White, Laura J; Simpson, Dennis A et al. (2003) An attenuating mutation in nsP1 of the Sindbis-group virus S.A.AR86 accelerates nonstructural protein processing and up-regulates viral 26S RNA synthesis. J Virol 77:1149-56 |
| Heise, M T; Simpson, D A; Johnston, R E (2000) Sindbis-group alphavirus replication in periosteum and endosteum of long bones in adult mice. J Virol 74:9294-9 |
| Heise, M T; Simpson, D A; Johnston, R E (2000) A single amino acid change in nsP1 attenuates neurovirulence of the Sindbis-group alphavirus S.A.AR86. J Virol 74:4207-13 |
