A5076763316- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Immunology Research
- Mitochondrial Function and Pathology
- Plant Virus Research Studies
- Herpesvirus Infections and Treatments
- Metabolomics and Mass Spectrometry Studies
- Metabolism and Genetic Disorders
- Synthesis and Biological Evaluation
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- Hepatitis Viruses Studies and Epidemiology
- Liver Diseases and Immunity
- Ubiquitin and proteasome pathways
- Birth, Development, and Health
- Zoonotic diseases and public health
- Genetic Associations and Epidemiology
- Click Chemistry and Applications
- Bioinformatics and Genomic Networks
- Synthesis and Characterization of Heterocyclic Compounds
- Plant Disease Resistance and Genetics
West China Medical Center of Sichuan University
2024
Boston University
2023-2024
University of Southern California
1983-2006
Southern California University for Professional Studies
1979-2006
Academia Sinica
2006
Fox Chase Cancer Center
1996
Howard Hughes Medical Institute
1990-1995
University of California, Los Angeles
1995
Scripps Research Institute
1994
The RNA genome of coronaviruses consists a single species nonsegmented RNA. In this communication, we demonstrate that the genomes different strains murine recombine during mixed infection at very high frequency. Susceptible cells were coinfected with temperature-sensitive mutant one strain mouse hepatitis virus (MHV) and wild-type strain. Of 21 randomly isolated viruses released from nonpermissive temperature, 2 recombinants which differed in site recombination. After three serial passages...
Hepatitis delta virus (HDV) contains a single-stranded circular RNA genome of 1.7 kilobases. In this report we demonstrate that subfragments HDV can undergo autocatalytic cleavage. This cleavage requires at least 500 microM Mg2+ or Ca2+, is not affected by varying the pH from 5.0 to 9.1, and occurs with fragments as small 133 nucleotides. The larger containing additional sequences have lower efficiency Deletion analysis both ends suggested catalytic ability resides in stretch no more than...
Mouse hepatitis virus, which replicates in cytoplasm, contains leader RNA sequences at the 5' end of virus-specific mRNAs. We have sequenced this by synthesizing cDNA from a synthetic oligodeoxyribonucleotide primer (15-mer) that is complementary to junction site between and body The on each mRNA exactly same size, span approximately equal 70 nucleotides. Leader fragments obtained several species were found be identical. Computer analysis shows they share extensive sequence homology with...
Mouse hepatitis virus A59 codes for seven mRNAs in infected cells. These are transcribed from a minus (-) strand template of genome length and contain leader RNA at their 5' ends. To further elucidate the mechanism coronavirus transcription, we examined structure mouse replicative intermediates (RIs) isolated by 2 M NaCl precipitation Sepharose 2-B column chromatography. Purified RIs migrated as single species on agarose gels sedimented between 12 38S 10 to 25% sucrose gradients. The...
Hepatitis delta antigen (HDAg) consists of two protein species 195 and 214 amino acids, respectively, which are identical in sequence except that the large HDAg has additional 19 acids at its C terminus is prenylated. Previous studies have shown surface hepatitis B virus (HBsAg) together can form empty (HDV) particles. To understand molecular mechanism HDV virion morphogenesis, we investigated possible direct protein-protein interaction between HBsAg. We constructed recombinant baculoviruses...
It has previously been shown that human hepatitis virus delta antigen an RNA-binding activity (Chang et al., J. Virol. 62:2403-2410, 1988). In the present study, specificity of such RNA-protein interaction was demonstrated by expressing various domains in Escherichia coli as TrpE fusion proteins and testing their activities a Northwestern protein-RNA immunoblot assay RNA gel mobility shift assay. Hepatitis (HDV) bound specifically to presence excess amount unrelated RNAs relatively high salt...
Four strains of the coronavirus murine hepatitis virus were examined for presence phosphorylated proteins. The nucleocapsid protein was determined to contain phosphate covalently linked serine but not threonine residues. only detected in these virus.
Mouse hepatitis virus (MHV), which replicates in cytoplasm of infected cells, contains an identical leader RNA sequence at the 5' end each virus-specific mRNAs. Previous studies suggested that synthesis these mRNAs does not involve conventional splicing and may instead require priming by a free RNA. In this communication, we demonstrate that, during mixed infection with two different MHVs, sequences from one could be detected on coinfecting high frequency, as if were joined together randomly...
The mouse hepatitis virus strain A59 codes for seven RNA species in the infected cells. These virus-specific RNAs were found to be polysome associated and therefore likely represent mRNA's. All of them have common 3'-end sequences (Lai et al., J. Virol. 39:823-834, 1981). Their structure was further studied with respect their 5'-end sequences. It that all these mRNA's contained cap structures at 5' ends. Furthermore, cap-containing oligonucleotides which immediately adjacent ends same most,...
Abstract Mitochondria carry their own circular genome and disruption of the mitochondrial is associated with various aging-related diseases. Unlike nuclear genome, DNA (mtDNA) can be present at 1000 s to 10,000 copies in somatic cells variants may exist a state heteroplasmy, where only fraction molecules harbors particular variant. We quantify mtDNA heteroplasmy 194,871 participants UK Biobank find that 1.5-fold increased risk all-cause mortality. Additionally, we functionally characterize...
Hepatitis delta antigen (HDAg) is an RNA-binding protein with binding specificity for hepatitis virus (HDV) RNA (J. H. Lin, M. F. Chang, S. C. Baker, Govindarajan, and Lai, J. Virol. 64:4051-4058, 1990). By amino acid sequence homology search, we have identified within its domain two stretches of arginine-rich motif (ARM), which present in many prokaryotic eukaryotic proteins. The first one KERQDHRRRKA the second EDEKRERRIAG, they are separated by 29 acids. Deletion either these ARM...
We have previously shown that most of the defective interfering (DI) RNA mouse hepatitis virus (MHV) are not packaged into virions. now identified, after 21 serial undiluted passages MHV, a small DI RNA, DIssF, which is efficiently The DIssF replicated at high efficiency on its transfection helper virus-infected cells. released from transfected cells interfered strongly with mRNA synthesis and growth virus. cDNA cloning sequence analysis revealed it 3.6 kb consists sequences derived five...
Simultaneous infection with hepatitis delta virus (HDV) and B (HBV) in humans is often associated severe viral liver disease including fulminant hepatitis. Since HBV thought to be noncytopathic the hepatocyte, enhanced severity observed during dual has been attributed either simultaneous immune responses against two viruses or direct cytotoxic effects of HDV products on hepatocyte both. To examine these alternate possibilities, we produced transgenic mice that express small large antigens...
Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods Results We performed cross-sectional prospective association analyses of blood-derived mtDNA CN outcomes in 27 316 participants 8 cohorts multiple racial ethnic groups with whole-genome sequencing. also Mendelian randomization to explore causal relationships coronary heart (CHD) cardiometabolic risk factors (obesity, diabetes, hypertension, hyperlipidemia).
Coronavirus mRNA is synthesized by a discontinuous transcription process, which involves free leader RNA species. As result, each virus-specific contains an identical derived from the 5', end of genomic RNA. In this study, we demonstrate primer extension studies that leader-fusion sites on given species coronavirus subgenomic are heterogeneous. The heterogeneity was due to variation in number pentanucleotide (UCUAA) repeats present at fusion site. This repeat region complementary between and...
Hepatitis delta antigen (HDAg) consists of two species, large (LHDAg) and small (SHDAg), which are identical in sequence except that the form contains 19 extra amino acids at C terminus. The is prenylated on Cxxx motif. can trans activate HDV RNA replication, while inhibits it. To determine molecular basis for their differential functions, we examined effects prenylation conformation function HDAg. We show presence prenylates masks a conformational epitope present SHDAg but hidden wild-type...
Previous studies suggested that coronavirus RNA transcription involves interaction between leader and the intergenic (IG) sequences, probably via protein-RNA interactions (X. M. Zhang, C.-L. Liao, C. Lai, J. Virol., 68:4738-4746, 1994; X. Zhang 68:6626-6633, 1994). To determine whether cellular proteins are involved in this process, we performed UV cross-linking experiments using cytoplasmic extracts of uninfected cells IG (promoter) sequence genes 6 7 (IG7) 5' untranslational region mouse...
The cytotoxic T lymphocyte (CTL) activity of spleen cells from BALB/c (H-2d) mice immunized with the neurotropic JHM strain mouse hepatitis virus (JHMV) was stimulated in vitro for 7 days. CTL were tested recognition target infected either JHMV or vaccinia recombinants expressing four structural proteins. Only recombinant nucleocapsid protein recognized. Cytotoxic cell lines established by limiting dilution brains undergoing acute demyelinating encephalomyelitis after infection JHMV. Twenty...
Hepatitis delta virus (HDV) RNA subfragments undergo self-cleavage at varying efficiencies. We have developed a procedure of using repeated cycles heat denaturation and renaturation to achieve high efficiency cleavage. This effect can also be achieved by gradual with or formamide. These results suggest that only subpopulation the catalytic molecules assumes active conformation required for self-cleavage. could general use detecting activities.
Improving our ability to understand and predict the dynamics of terrestrial carbon cycle remains a pressing challenge despite rapidly growing volume diversity Earth Observation data. State data assimilation represents path forward via an iterative making process-based forecasts then statistically reconciling these against numerous ground-based remotely-sensed constraints into “reanalysis” product that provides full spatiotemporal budgets with robust uncertainty accounting. Here we report on...
The alcohol-associated biological aging remains to be studied across adulthood. We conducted linear regression analyses investigate the associations between alcohol consumption and two DNA methylation-based age acceleration metrics in 3823 Framingham Heart Study participants (24–92 years 53.8% women) adjusting for covariates. also investigated whether epigenetic mediated association of with hypertension. found that higher long-term average was significantly associated assessed by GrimAge...
Hepatitis delta virus (HDV) is hepatotropic and frequently causes fulminant hepatitis in both human nonhuman primate hosts. To understand the molecular basis of HDV tissue tropism mechanism pathogenesis, transgenic mice which replication-competent dimeric RNA expressed under control either liver-specific or universal transcriptional promoters were developed. The replicated efficiently liver several tissues nonhepatic origin. Surprisingly, maximal replication occurred skeletal muscle was...