Investigation of the mixed origins of the MGC-803 cell line reveals that it is a hybrid cell line derived from HeLa.

Human cancer cell lines have an essential role in cancer research, but only authentic cell lines should be used as biological models. Authentication testing using short tandem repeat (STR) loci has shown that MGC-803 cells, which were reported to come from gastric adenocarcinoma, are similar to HeLa. In this study, we confirmed that the MGC-803 cell line contains genetic material from HeLa, including genetic sequence from human papilloma virus 18 (HPV18). Additional alleles were present on STR analysis that remained stable after extensive passaging and generation of mono-clones. This behavior is consistent with a hybrid cell line arising from cell-cell fusion. Further genetic analysis revealed that MGC-803 originated from donors with different genetic ancestries, one African (HeLa) and the other Asian. Transcriptomic analysis demonstrated that MGC-803 closely resembles HeLa and another nasopharyngeal-HeLa hybrid cell line CNE-2. Based on these findings, we conclude that MGC-803 is a hybrid cell line derived from HeLa and other cells, the latter derived from a different patient with Asian genetic ancestry.

Virus-like particle vaccine comprised of the HA, NA, and M1 proteins of an avian isolated H5N1 influenza virus induces protective immunity against homologous and heterologous strains in mice.

Highly pathogenic avian influenza H5N1 virus represents a growing threat for an influenza pandemic. Development of effective vaccines for H5N1 is a priority for pandemic preparedness. Focusing on influenza virus-like particles (VLPs) has been suggested as a promising vaccine approach. Recent VLP vaccination efforts have been concentrated on the H5N1 strains isolated from humans. Because all confirmed cases of human H5N1 infection were directly transmitted from infected poultry, it is of interest to develop VLP vaccines comprised of antigenic proteins of avian H5N1 strains in order to compare their efficacy in fighting diverse H5N1 strains with vaccines developed using human isolates. In this study, we generated a VLP vaccine composed of the HA, NA, and M1 proteins of the avian H5N1 influenza virus isolate A/chicken/Hubei/489/2004, which seems to occupy a unique phylogenetic position; it belongs to neither clade 1 nor clade 2. Upon infection of Sf9 insect cells using recombinant baculoviruses, the co-expressed HA, NA, and M1 proteins self-assembled and released into the culture medium as VLPs. In a mouse model, purified VLPs elicited an effective antibody response and conferred complete protection against heterologous human H5N1 influenza virus, as well as a homologous avian H5N1 influenza virus isolate. Our work provides further evidence that vaccination with influenza VLPs may be a productive approach to achieve protection against diverse H5N1 strains.

An antiviral mechanism investigated with ribavirin as an RNA virus mutagen for foot-and-mouth disease virus.

To prove whether error catastrophe/lethal mutagenesis is the primary antiviral mechanism of action of ribavirin against foot-and-mouth disease virus (FMDV). Ribavirin passage experiments were performed and supernatants of Rp1 to Rp5 were harvested. Morphological alterations as well as the levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected using the supernatants of Rp1 to Rp5 and control were measured by microscope, real-time RT-PCR, western-blotting and plaque assays, respectively. The mutation frequency was measured by sequencing the complete P1- and 3D-encoding region of FMDV after a single round of virus infection from ribavirin-treated or untreated FMDV-infected cells. Ribavirin treatment for FMDV caused dramatically inhibition of multiplication in cell cultures. The levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected were more greatly reduced along with the passage from Rp1 to Rp5, moreover, nucleocapsid protein could not be detected and no recovery of infectious virus in the supernatant or detection of intracellular viral RNA was observed at the Rp5-infected cells. A high mutation rate, giving rise to an 8-and 11-fold increase in mutagenesis and resulting in some amino acid substitutions, was found in viral RNA synthesized at a single round of virus infection in the presence of ribavirin of 1000 microM and caused a 99.7% loss in viral infectivity in contrast with parallel untreated control virus. These results suggest that the antiviral molecular mechanism of ribavirin is based on the lethal mutagenesis/error catastrophe, that is, the ribavirin is not merely an antiviral reagent but also an effective mutagen.