Identification and Characterization of a Ross River Virus Variant That Grows Persistently in Macrophages, Shows Altered Disease Kinetics in a Mouse Model, and Exhibits Resistance to Type I Interferon

被引：20

作者：

Lidbury, Brett A. ^{[2
]}

Rulli, Nestor E. ^{[1
,2
,3
,4
]}

Musso, Cristina M. ^{[2
]}

Cossetto, Susan B. ^{[2
]}

Zaid, Ali ^{[2
,3
]}

Suhrbier, Andreas ^{[5
,6
]}

Rothenfluh, Harald S. ^{[7
]}

Rolph, Michael S. ^{[1
,2
]}

Mahalingam, Suresh ^{[1
,2
,3
]}

机构：

[1] Griffith Univ, Emerging Viruses & Inflammat Res Grp, Inst Glyc, Gold Coast, Qld 4222, Australia

[2] Univ Canberra, Virus & Inflammat Res Grp, Fac Sci Appl, Canberra, ACT 2601, Australia

[3] Univ Wollongong, Virus & Inflammat Res Grp, Sch Biol Sci, Wollongong, NSW 2522, Australia

[4] Univ Nacl La Plata, LISIN, Fac Ciencias Exactas, Buenos Aires, DF, Argentina

[5] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[6] Griffith Univ, Brisbane, Qld 4111, Australia

[7] Australian Natl Univ, Div Immunol & Genet, John Curtin Sch Med Res, Canberra, ACT 0200, Australia

来源：

JOURNAL OF VIROLOGY | 2011年 / 85卷 / 11期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

VENEZUELAN EQUINE ENCEPHALITIS; MYELOID DENDRITIC CELLS; STRAND RNA VIRUSES; WEST-NILE-VIRUS; CHIKUNGUNYA VIRUS; GENE-EXPRESSION; NONSTRUCTURAL PROTEIN-2; ARTHROGENIC ALPHAVIRUS; ALPHA/BETA INTERFERONS; DEPENDENT ENHANCEMENT;

D O I：

10.1128/JVI.01189-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Alphaviruses, such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV), cause outbreaks of human rheumatic disease worldwide. RRV is a positive-sense single-stranded RNA virus endemic to Australia and Papua New Guinea. In this study, we sought to establish an in vitro model of RRV evolution in response to cellular antiviral defense mechanisms. RRV was able to establish persistent infection in activated macrophages, and a small-plaque variant (RRVPERS) was isolated after several weeks of culture. Nucleotide sequence analysis of RRVPERS found several nucleotide differences in the nonstructural protein (nsP) region of the RRVPERS genome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRVPERS showed significantly enhanced resistance to beta interferon (IFN-beta)-stimulated antiviral activity. RRVPERS infection of RAW 264.7 macrophages induced lower levels of IFN-beta expression and production than infection with RRV-T48. RRVPERS was also able to inhibit type I IFN signaling. Mice infected with RRVPERS exhibited significantly enhanced disease severity and mortality compared to mice infected with RRV-T48. These results provide strong evidence that the cellular antiviral response can direct selective pressure for viral sequence evolution that impacts on virus fitness and sensitivity to alpha/beta IFN (IFN-alpha/beta).

引用

页码：5651 / 5663

页数：13