Publications by authors named "Joseph K-K Li"

The human parainfluenza virus type 3 (HPIV3) phosphoprotein (P) gene is unusual as it contains an editing site where nontemplated ribonucleotide residues can be inserted. This RNA editing can lead to the expression of the viral P, PD, putative W, and theoretical V protein from a single gene. Although the HPIV3 PD protein has been detected, its function and those of the W and V proteins are poorly understood.

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Bluetongue virus (BTV) genome contains ten double-stranded RNA segments. The sequence of the plus strand of each of the BTV genomic double-stranded RNAs is the same as that of its mRNA, which encodes for a single viral protein, except the smallest S4 segment which can encode for two nonstructural proteins, primarily for the release assistance of the viral progeny. The separation and isolation of each BTV dsRNA segment and viral protein have provided extensive data related to its viral infection, pathology, suppression of host cellular functions, and eventual apoptosis of the infected host cells.

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As an obligate intracellular parasite, the genome of the Bluetongue virus (BTV) contains ten double-stranded RNA segments which are encapsidated by viral proteins, forming "transport vesicles" that can transmit the viral progeny cell-to-cell efficiently and that can also be transmitted animal-to-animal by a biting midge. BTV is a cytoplasmic virus, and its five major steps of viral infection: attachment, entry, uncoating, assembly, and release, occur only in the cytosol within the infected host cell. Viral replication, suppression of cellular processes, and subsequent pathological damage disrupt many cellular pathways, leading to cellular apoptosis.

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Humans are sero-negative toward bluetongue viruses (BTVs) since BTVs do not infect normal human cells. Infection and selective degradation of several human cancer cell lines but not normal ones by five US BTV serotypes have been investigated. We determined the susceptibilities of many normal and human cancer cells to BTV infections and made comparative kinetic analyses of their cytopathic effects, survival rates, ultra-structural changes, cellular apoptosis and necrosis, cell cycle arrest, cytokine profiles, viral genome, mRNAs, and progeny titers.

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Article Synopsis
  • Urtica dioica agglutinin (UDA) is a small lectin that shows potent antiviral effects against SARS-CoV strains, significantly reducing virus replication in cell cultures and in a mouse model.
  • In mice treated with UDA, there was a 90% reduction in viral loads and significant protection against weight loss, indicating a therapeutic potential for treating SARS infections.
  • UDA seems to work by targeting early stages of the viral replication cycle, specifically inhibiting the virus's ability to bind and penetrate host cells.
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  • - Interferons (IFNs) play a critical role in the immune response to viral infections, and research explores the adenovirus vectored mouse IFN alpha gene (mDEF201) as a potential treatment for SARS-CoV in mice.
  • - Mice that received intranasal doses of mDEF201 before exposure to deadly SARS-CoV displayed complete protection and maintained normal body weight post-infection, indicating its effectiveness.
  • - The study found that mDEF201 provided protective effects on the lungs in a dose-dependent manner, suggesting it could be a promising new antiviral treatment for SARS-CoV infections.
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The ability to rescue an infectious, recombinant RNA virus from a cDNA clone has led to new opportunities for measuring viral replication from a viral expressed reporter gene. In this protocol, the process of inserting the enhanced green fluorescent protein (EGFP) gene into the human parainfluenza virus type 3 (HPIV-3) antigenome and rescuing a recombinant, infectious virus is described. The first step in this process includes the generation of a cDNA clone copied from viral RNA isolated from an HPIV-3 wild-type infection.

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The ability to rescue an infectious, recombinant, negative-stranded, RNA virus from a complementary DNA (cDNA) clone, has led to new opportunities for measuring viral replication from a viral expressed reporter gene. In this study, the enhanced green fluorescent protein (EGFP) gene was inserted into the human parainfluenza virus type 3 (HPIV-3) antigenome and a recombinant, infectious virus was rescued. Maximum EGFP expression levels, measured by fluorescence, were seen at day 3.

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Phenothiazine and derivatives were tested for inhibition of SARS-CoV replication. Phenothiazine slightly inhibited SARS-CoV replication in a neutral red (NR) uptake assay. Adding a propylamino group to give promazine reduced virus yields (VYR assay) with an EC(90)=8.

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Bluetongue viruses (BTVs) infect primarily domestic cattle and wild ruminants but have never been shown to infect normal human cells. Thus, humans are sero-negative towards BTVs. The selective and differential effects of BTV serotype 10 (BTV-10) infection were investigated with five cell lines including primary human embryo lung fibroblast (HEL) and primary murine embryos fibroblast(MEF), human hepatic carcinoma 3B cell line (Hep-3B), human lung carcinoma cell line (A549) and mouse fibroblast cell line (NIH 3T3).

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Because of the conflicting data concerning the SARS-CoV inhibitory efficacy of ribavirin, an inosine monophosphate (IMP) dehydrogenase inhibitor, studies were done to evaluate the efficacy of ribavirin and other IMP dehydrogenase inhibitors (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), mizoribine, and mycophenolic acid) in preventing viral replication in the lungs of BALB/c mice, a replication model for severe acute respiratory syndrome (SARS) infections (Subbarao, K., McAuliffe, J., Vogel, L.

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