Pathogenesis and transmission of SARS-CoV-2 D614G, Alpha, Gamma, Delta, and Omicron variants in golden hamsters.

Since the emergence of SARS-CoV-2 in humans, novel variants have evolved to become dominant circulating lineages. These include D614G (B.1 lineage), Alpha (B.

Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9.

Major histocompatibility complex class I (MHC-I) molecules play a critical role in the host's antiviral response by presenting virus-derived antigenic peptides to cytotoxic T lymphocytes (CTLs), enabling the clearance of virus-infected cells. Human adenoviruses evade CTL-mediated cell lysis, in part, by interfering directly with the MHC-I antigen presentation pathway through the expression of E3-19K, which binds both MHC-I and the transporter associated with antigen processing protein and sequestering MHC-I within the endoplasmic reticulum. Fowl adenoviruses have no homologues of E3-19K.

Fowl adenovirus 9 ORF19, a lipase homolog, is nonessential for virus replication and is suitable for foreign gene expression.

Fowl adenovirus 9 (FAdV-9) has one of the largest genomes (45 kb) so far sequenced from all adenoviruses studied. Genus-specific genes located within the early (E) regions at the right and left ends of the viral genome have unknown functions except for ORF8 (Gam-1 gene), ORF22 and ORF1 (dUTPase gene). ORF19, located at the right end of the genome (nts 34,220-36,443), is predicted to encode a lipase protein and its homologs are also found in all FAdV genomes so far sequenced.

Fowl Adenovirus 4 (FAdV-4)-Based Infectious Clone for Vaccine Vector Development and Viral Gene Function Studies.

Fowl adenovirus 4 (FAdV-4) is associated with economically important poultry diseases. Recent studies of fully sequenced genomes of FAdV-4 isolates suggest potential genomic regions associated with virulence and amenable for manipulation and vector development. Direct manipulation of viral genomes is cumbersome, as opposed to that of infectious clones-viral genomes cloned into plasmid or cosmid vectors.

Amplified visual immunosensor integrated with nanozyme for ultrasensitive detection of avian influenza virus.

Nanomaterial-based artificial enzymes or nanozymes exhibit superior properties such as stability, cost effectiveness and ease of preparation in comparison to conventional enzymes. However, the lower catalytic activity of nanozymes limits their sensitivity and thereby practical applications in the bioanalytical field. To overcome this drawback, herein we propose a very simple but highly sensitive, specific and low-cost dual enhanced colorimetric immunoassay for avian influenza A (H5N1) virus.

Foreign gene expression and induction of antibody response by recombinant fowl adenovirus-9-based vectors with exogenous promoters.

Fowl adenoviruses (FAdVs) are promising vectors for poultry vaccines and gene therapy. The commonly used human cytomegalovirus (CMV) promoter in recombinant FAdV-9 viruses (recFAdV-9s) leads to foreign gene expression that elicits an antibody response. Despite its strength, studies have shown that the CMV promoter is prone to silencing by methylation hampering the in vivo application of vectors containing this promoter.

Replication and Oncolytic Activity of an Avian Orthoreovirus in Human Hepatocellular Carcinoma Cells.

Oncolytic viruses are cancer therapeutics with promising outcomes in pre-clinical and clinical settings. Animal viruses have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. We isolated an avian orthoreovirus (ARV-PB1), and tested it against a panel of hepatocellular carcinoma cells.

Fowl Adenovirus-Based Vaccine Platform.

Nonpathogenic fowl adenoviruses (FAdVs) are amenable for engineering multivalent vaccine platforms due to large stretches of nonessential DNA sequences in their genomes. We describe the generation of FAdV-9-based vaccine platforms by targeted homologous recombination in an infectious clone (pPacFAdV-9 or wild type FAdmid) containing the entire viral genome in a cosmid vector. The viral DNA is subsequently released from the cosmid by restriction enzyme digestion followed by transfection in a chicken hepatoma cell line (CH-SAH).

N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells.

N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state.

Antibody response and virus shedding of chickens inoculated with left end deleted fowl adenovirus 9-based recombinant viruses.

The nonpathogenic fowl adenoviruses (FAdVs) are suitable recombinant virus vectors. Two different replication-competent FAdV-9-based recombinant viruses carrying the enhanced green fluorescent protein (EGFP) gene within a nonessential DNA sequence at the left end genomic region were tested in chickens to study the antibody response by enzyme-linked immunosorbent assay to both the foreign proteins, EGFP and FAdV-9, and virus shedding through the feces. All inoculations were done intramuscularly: groups 1 and 2 with the recombinant viruses and group 3 with the wild-type FAdV-9 virus.

Oncolytic viruses as experimental treatments for malignant gliomas: using a scourge to treat a devil.

The concept of oncolytic viral therapy has a century-old history, but only within the last 20 years have oncolytic viruses been considered for the treatment of brain cancers. Viruses such as herpes, measles, and vaccinia have all been known to cause devastating cases of neurological disease in humans, yet these 'scourges' are now being harnessed in such a way that they prove very useful as cancer therapeutics. There have been 8 formal clinical trials and 3 case studies using oncolytic viruses to treat malignant glioma patients.

The non-essential left end region of the fowl adenovirus 9 genome is suitable for foreign gene insertion/replacement.

The goals of this study were to demonstrate that a non-essential region at the left end of the fowl adenovirus 9 (FAdV-9) genome could be used to generate recombinant viruses, examine their in vitro growth characteristics and determine their ability to transduce non-avian cells. Three FAdV-9 vectors (rFAdV-9s) were generated carrying the enhanced-green fluorescent protein (EGFP) gene: FAdV-9inEGFP, FAdV-9 Delta 1-EGFP and FAdV-9 Delta 4-EGFP. FAdV-9inEGFP carried the EGFP cassette inserted into the non-essential region without deletion resulting in an increase of the genome size to 103.

A region at the left end of the fowl adenovirus 9 genome that is non-essential in vitro has consequences in vivo.

The regions at the left and right ends of fowl adenovirus (FAdV) genomes are not well-characterized in comparison to those of human adenoviruses. Using a series of deletion mutants, we analysed a 2.4 kb region near the left end of the FAdV-9 genome (nt 400-2782) that contains packaging-signal motifs VI and VII and open reading frames (ORFs) 0, 1, 1A, 1B, 1C and 2.

Detection and quantitation of fowl adenovirus genome by a real-time PCR assay.

The purpose of the study was to develop a highly sensitive real-time polymerase chain reaction (PCR) assay to detect and quantitate fowl adenovirus (FAdV) DNA in chicken tissues, using FAdV-9 as a model. The assay had a dynamic range of 7 logs and minimum detection limit of 9.4 viral genome copies.

Sequence comparison of the right end of fowl adenovirus genomes.

The nucleotide sequence at the right end of the genomes of fowl adenoviruses (FAdVs) representing species groups C (FAdV-4 CA and FAdV-10 C-2B), D (FAdV-2 CA), and E (FAdV-8 CA) was determined and analyzed and compared to FAdV-1 (species group A virus) and FAdV-9 A-2A (species group B virus). High nucleotide sequence identities and amino acid identities (74-94%) were found among viruses in the same species group. Homologues to known open reading frames (ORFs) of the right end of the reported FAdV genomes, such as lipase and Gam-1, were also found in all analyzed viral genomes.

Sequence analysis of the left end of fowl adenovirus genomes.

Nucleotide sequence analysis of the left end of the genome of fowl adenoviruses (FAdV) representing species group C (FAdV-4 and -10), D (FAdV-2) and E (FAdV-8) were carried out, and the sequence data was compared to those of FAdV-1 (FAdV-A) and FAdV-9 (FAdV-D). The viruses were propagated in chicken hepatoma cell line for viral DNA isolation. Restriction endonuclease analysis was performed followed by hybridization with two DNA probes representing the left end of FAdV-9.