Function of the small hydrophobic protein of J paramyxovirus.
At 18,954 nucleotides, the J paramyxovirus (JPV) genome is one of the largest in the family Paramyxoviridae, consisting of eight genes in the order 3'-N-P/V/C-M-F-SH-TM-G-L-5'. To study the function of novel paramyxovirus genes in JPV, a plasmid containing a full-length cDNA clone of the genome of JPV was constructed. In this study, the function of the small hydrophobic (SH) protein of JPV was examined by generating a recombinant JPV lacking the coding sequence of the SH protein (rJPVΔSH). rJPVΔSH was viable and had no growth defect in tissue culture cells. However, more tumor necrosis factor alpha (TNF-α) was produced during rJPVΔSH infection, suggesting that SH plays a role in inhibiting TNF-α production. rJPVΔSH induced more apoptosis in tissue culture cells than rJPV. Virus-induced apoptosis was inhibited by neutralizing antibody against TNF-α, suggesting that TNF-α contributes to JPV-induced apoptosis in vitro. The expression of JPV SH protein inhibited TNF-α-induced NF-κB activation in a reporter gene assay, suggesting that JPV SH protein can inhibit TNF-α signaling in vitro. Furthermore, infection of mice with rJPVΔSH induced more TNF-α expression, indicating that SH plays a role in blocking TNF-α expression in vivo.
Li
Zhuo
Z
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, 501 D. W. Brooks Drive, Athens, GA 30602, USA.
Xu
Jie
J
Patel
Jui
J
Fuentes
Sandra
S
Lin
Yuan
Y
Anderson
Danielle
D
Sakamoto
Kaori
K
Wang
Lin-Fa
LF
He
Biao
B
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002522:Chlorocebus aethiops; D007739:L Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018184:Paramyxoviridae Infections / Q000378:metabolism / Q000821:virology*; D018098:Paramyxovirinae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014709:Vero Cells; D010948:Viral Plaque Assay
D016328:NF-kappa B; D015682:Retroviridae Proteins, Oncogenic; D014409:Tumor Necrosis Factor-alpha; C056150:small hydrophobic protein, virus