ABSTRACT
The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.
Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Eutheria/virology , Evolution, Molecular , Genome, Viral/genetics , Sequence Homology, Nucleic Acid , Amino Acid Sequence , Animals , Betacoronavirus/chemistry , Betacoronavirus/classification , COVID-19 , China/epidemiology , Chiroptera/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Reservoirs/virology , Genomics , Humans , Malaysia , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Recombination, Genetic , SARS-CoV-2 , Sequence Alignment , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Zoonoses/virologyABSTRACT
To assess herd immunity to swine influenza viruses, we determined antibodies in 28 paired serum samples from participants in a prospective serologic cohort study in Hong Kong who had seroconverted to pandemic (H1N1) 2009 virus. Results indicated that infection with pandemic (H1N1) 2009 broadens cross-reactive immunity to other recent subtype H1 swine viruses.
Subject(s)
Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/immunology , Orthomyxoviridae Infections/immunology , Adolescent , Adult , Aged , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Child , Cross Reactions , Hong Kong/epidemiology , Humans , Influenza, Human/epidemiology , Middle Aged , Orthomyxoviridae Infections/epidemiology , Pandemics , Swine/virology , Young AdultABSTRACT
In cancer research, autophagy acts as a doubleedged sword: it increases cell viability or induces cell apoptosis depending upon the cell context and functional status. Recent studies have shown that adenosine (Ado) has cytotoxic effects in many tumors. However, the role of autophagy in Adoinduced apoptosis is still poorly understood. In the present study, Adoinduced apoptotic death and autophagy in hepatoblastoma HepG2 cells was investigated and the relationship between autophagy and apoptosis was identified. In the present study, it was demonstrated that Ado inhibited HepG2 cell growth in a time and concentrationdependent manner and activated endoplasmic reticulum (ER) stress, as indicated by G0/G1 cell cycle arrest, the increased mRNA and protein levels of GRP78/BiP, PERK, ATF4, CHOP, cleaved caspase3, cytochrome c and the loss of mitochon-drial membrane potential (ΔΨm). Ado also induced autophagic flux, revealed by the increased expression of the autophagy marker microtubuleassociated protein 1 light chain 3II (LC3II), Beclin1, autophagosomes, and the degradation of p62, as revealed by western blot analysis and macrophagederived chemokine (MDC) staining. Blocking autophagy using LY294002 notably entrenched Adoinduced growth inhibition and cell apoptosis, as demonstrated with the increased expression of cytochrome c and p62, and the decreased expression of LC3II. Conversely, the autophagy inducer rapamycin alleviated Adoinduced apoptosis and markedly increased the ΔΨm. Moreover, knockdown of AMPK with siAMPK partially abolished Adoinduced ULK1 activation and mTOR inhibition, and thus reinforced CHOP expression and Adoinduced apoptosis. These results indicated that Adoinduced ER stress resulted in apoptosis and autophagy concurrently. The AMPK/mTOR/ULK1 signaling pathway played a protective role in the apoptotic procession. Inhibition of autophagy may effectively enhance the anticancer effect of Ado in human hepatoblastoma HepG2 cells.
Subject(s)
Adenosine/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Hepatoblastoma/drug therapy , Liver Neoplasms/drug therapy , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Adenosine/therapeutic use , Autophagy-Related Protein-1 Homolog/metabolism , Cell Survival/drug effects , Chromones/pharmacology , Dose-Response Relationship, Drug , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Gene Knockdown Techniques , Hep G2 Cells , Hepatoblastoma/pathology , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Liver Neoplasms/pathology , Morpholines/pharmacology , RNA, Small Interfering/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolismABSTRACT
Bat coronaviruses (Bt-CoVs) are thought to be the precursors of severe acute respiratory syndrome coronavirus. We detected Bt-CoVs in 2 bat species from Trinidad. Phylogenetic analysis of the RNA-dependent RNA polymerase gene and helicase confirmed them as group 1 coronaviruses.
Subject(s)
Chiroptera/virology , Coronavirus Infections/veterinary , Coronavirus , Phylogeny , Animals , Coronavirus/classification , Coronavirus/genetics , Coronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Molecular Sequence Data , RNA, Viral/analysis , RNA-Dependent RNA Polymerase/genetics , Sequence Analysis, DNA , South America/epidemiology , Trinidad and Tobago/epidemiologyABSTRACT
Astroviruses infect humans and many different animal species and are associated with gastroenteritis. Recent studies first detected the virus from bat species in Hong Kong. To understand astrovirus distribution in the wider region further, we examined the prevalence of this virus family in bat specimens collected from a large geographical region of mainland China. We collected 500 anal swabs from 20 bat species in 51 natural habitats from 11 provinces of China and tested these for astroviruses. Our study revealed a remarkably high genetic diversity of astroviruses; five monophyletic groups were identified in bats, including two novel groups. Evidence for varying degrees of host restriction for astroviruses from bats has been found. Phylogenetic analyses also provided insight into the inter-species transmission of Mamastrovirus.