No abstract

Since the beginning of the 20th century, humans have experienced four influenza pandemics, including the devastating 1918 'Spanish influenza'. Moreover, H5N1 highly pathogenic avian influenza (HPAI) viruses are currently spreading worldwide, although they are not yet efficiently transmitted among humans. While the threat of a global pandemic involving a highly pathogenic influenza virus strain looms large, our mechanisms to address such a catastrophe remain limited. Here, we show that pre-stimulation of Toll-like receptors (TLRs) 2 and 4 increased resistance against influenza viruses known to induce high pathogenicity in animal models. Our data emphasize the complexity of the host response against different influenza viruses, and suggest that TLR agonists might be utilized to protect against lethality associated with highly pathogenic influenza virus infection in humans.

Purpose: To investigate the specific role of immune responses induced by lentogenic Newcastle disease virus (NDV) for its antitumor effect. Materials and methods: NDV LaSota strain was used to infect the following human cells: non-small cell lung carcinoma (A549), glioblastoma (U87MG and T98G), mammary gland adenocarcinoma (MCF7 and MDA-MB-453), hepatocellular carcinoma (Huh7), transformed embryonic kidney cells (HEK293), primary monocytes, lung fibroblast (HF19), skin fibroblast (NB1RGB) and rat astroglia (RCR-1) at 0.001 multiplicity of infection. NDV-induced cytotoxicity and expression of proinflammatory cytokines were analyzed using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and multiplex enzyme-linked immunosorbent assay, respectively. Results: Tumor cells (A549, U87MG, T98G, Huh7, MDA-MB-453, and MCF7) showed viability of <44%, while normal cell lines HEK293, NB1RGB, and RCR-1 showed 84%, 73%, and 69% viability at 72 hours postinfection, respectively. Proinflammatory cytokine profiling showed that NDV mainly induced the secretion of interferon (IFN)-α, IFN-β, and IFN-λ in tumor cells and only IFN-λ in normal cells. In addition, NDV infection induced the production of interleukin (IL)-6 in most cells. Conclusion: Our findings suggest a new perspective regarding the role of IFN-λ and IL-6 in the mechanism of tumor selectivity and oncolysis of NDV. Keywords: Newcastle disease virus, oncolytic virus, interferons, cytokines IntroductionEvery year, mortality caused by cancer is increasing globally. This calls for novel therapeutic strategies.1 Use of oncolytic viruses represents a class of promising antitumor therapeutic options, primarily through the direct lysing of cancer cells and secondarily through the potential antitumor response induced by inflammation. [2][3][4][5][6] Newcastle disease virus (NDV) is a negative-strand RNA virus from the family Paramyxoviridae. This virus has been reported to be an effective oncolytic agent in vitro and in vivo against many types of solid tumors such as hepatocellular carcinoma, pancreatic adenocarcinoma, melanoma, pleural mesothelioma, colorectal carcinoma, renal carcinoma, glioblastoma and many others, 5,7-13 as well as in clinical studies in patients with glioblastoma multiforme, colorectal carcinoma, non-small cell lung carcinoma, renal carcinoma, breast adenocarcinoma, mesothelioma and pancreatic adenocarcinoma.14-18 NDV causes a disease that predominantly affects poultry, although infection in humans has been reported to cause conjunctivitis 19,20 and/or mild flu-like symptoms. [13][14][15][16][17]21 Based on their virulence on birds, NDV strains can be divided into 23-27 NDV is postulated to be a potent type I IFN inducer, but due to defective IFN signaling in tumor cells NDV replicates better in tumor cells. This has been the basis of tumor selective replication of NDV. 11,18,[28][29][30][31] The evidence for type I IFN production in vitro and in vivo after NDV infection has been obtained by measuring the level of IFN-α/β and the induction...

Background and Aim: Existing data on the characteristics of infectious bronchitis virus (IBV) gathered throughout Indonesia have been recognized to indicate variants similar to globally distributed vaccine strains. Despite past and current intensive vaccination programs, IBV infections in the country's poultry industry have not been effectively controlled. Therefore, this study aimed to investigate the genotype of several isolates based on partial S1 gene sequences. In particular, the investigation is directed to focus on layer chickens in actively vaccinated farms indicating IBV symptoms. Materials and Methods: Samples were isolated from ten different layer chicken flocks experiencing respiratory problem, drops in egg production, and a "penguin-like" stance, which were collected from commercial poultry farms in Central Java and Yogyakarta regions, Indonesia, within the periods of 2012-2018. Fragment of the S1 gene of IBV sampled from actively vaccinated commercial poultry farms was amplified using primer 5'-aca tgg taa ttt ttc aga tgg-3' (forward) and 5'-cag att gct tac aac cac c-3' (reverse) with the length of polymerase chain reaction (PCR) product at 383 bp. The sequence of samples was then compared with the sequence of reference S1 gene nucleotides of IBV from NCBI GenBank database. The amino acid analysis and multiple alignment sequence were conducted using Mega X. Results: During necropsy, enlargement of the oviduct and swollen kidney were observed. Reverse transcription-PCR diagnosis of their 383 bp S1 gene showed that all samples were IBV positive. Phylogenetic analysis of the S1 gene discovered seven samples to be clustered as 4/91-like strains. Meanwhile, the remaining three samples were grouped in QX-like strain cluster. Conclusion: This study is a pioneering report providing molecular evidence of pathogenic QX-like and 4/91-like strains circulating in Indonesia. Findings discovered, in this study, strongly suggested the importance of improving protections by available IBV vaccines through updated circulating strain clusters. It is critical to ensure the delivery of an effective control measurement of and vaccination protocols against IBV infections in the country's commercial poultry industry in particular and worldwide in general.

Newcastle disease virus (NDV) strongly induces both type I and III antiviral interferons (IFNs-α/-β and IFN-λ, respectively) in tumor cells while it induces mainly type III IFN in normal cells. Impairment of antiviral type I IFN signaling in tumor cells is thought to be the reason for effective oncolysis. However, there is lack of clarity why lentogenic strain NDV can also induce oncolysis. NDV infection caused apoptosis in normal and tumor cells as demonstrated with the caspase-3 enzyme activation and annexin-V detection. The apoptosis response was inhibited by B18R protein (a type I IFN inhibitor) in tumor cells i.e. A549 and U87MG, and not in normal cells i.e. NB1RGB and HEK293. Similarly, UV-inactivated medium from NDV infection was shown to induce apoptosis in corresponding cells and the response was inhibited in A549 and U87MG cells with the addition of B18R protein. Treatment with combination of IFNs-α/-β/-λ or IFNs-α/-β or IFN-λ in NB1RGB, HEK293, A549 and U87MG showed that caspase activity in IFNs-α/-β/-λ group was the highest, followed with IFN-α/-β group and IFN-λ group. This suggests that tumor-selectivity of NDV is mainly because of the cumulative effect of type I and III in tumor cells that lead to higher apoptotic effect.