Naturally-occurring porphyrins in a spontaneous-tumour bearing mouse model

2011 ◽  
Vol 10 (7) ◽  
pp. 1189 ◽  
Author(s):  
Anna Cleta Croce ◽  
Gerardo Santamaria ◽  
Uliana De Simone ◽  
Franco Lucchini ◽  
Isabel Freitas ◽  
...  
2018 ◽  
Vol 59 (15) ◽  
pp. 6102 ◽  
Author(s):  
Mark M. Hassall ◽  
Alun R. Barnard ◽  
Harry O. Orlans ◽  
Michelle E. McClements ◽  
Peter Charbel Issa ◽  
...  

1983 ◽  
Vol 69 (6) ◽  
pp. 489-496 ◽  
Author(s):  
Vimal Suhas Aroskar ◽  
Chintamani Shankar Godbole ◽  
Kamlakar Anant Chaubal

The nonadherent splenic cells from normal and tumour-bearing (mouse fibrosarcoma-MFS) Swiss mice were divided into 6 subpopulations on Percoll step density gradient and characterised. For the determination of their cytotoxicity towards syngeneic MFS cells and their electrophoretic mobility (EPM), the splenic cell populations were pooled to form 2 broad groups: a lower-density group (density of saline to just < 1.069 g/ml) and a higher-density group (1.069 to just < 1.087 gm/ml). In general, the splenic cells from mice bearing 10- to 11-day-old MFS tumours differed in certain characteristics from those of normal mice in that they showed an increase in the following: proliferation, heterogeneity, with appearance of large cells (>70 μ2); cells with a lower density (< 1.069 g/ml); cells with a lower (< 0.85 μ/sec/Volt/cm) anodi cEPM. The cytotoxicity studies revealed that: a) the lower-density splenic cells of both normal and tumour-bearing mice were more cytotoxic than the higher-density splenic cells; b) the lower- and higher-density splenic cells of tumour-bearing mice were more cytotoxic than the corresponding cells of normal mice. These findings indicate that the splenic cells of mice with a lower EPM and a lower density are the main contributors of cell-mediated cytolysis of a subpopulation of MFS cells.


2019 ◽  
Vol 93 (22) ◽  
Author(s):  
Szu-Yao Wu ◽  
Ya-Shu Chang ◽  
Tien-Hua Chu ◽  
Chiaho Shih

ABSTRACT Hepatitis B virus (HBV) core protein (HBc) accumulates frequent mutations in natural infection. Wild-type HBV is known to secrete predominantly virions containing mature DNA genome. However, a frequent naturally occurring HBc variant, I97L, changing from an isoleucine to a leucine at amino acid 97, exhibited an immature secretion phenotype in culture, which preferentially secretes virions containing immature genomes. In contrast, mutant P130T, changing from a proline to a threonine at amino acid 130, exhibited a hypermaturation phenotype by accumulating an excessive amount of intracellular fully mature DNA genome. Using a hydrodynamic delivery mouse model, we studied the in vivo behaviors of these two mutants, I97L and P130T. We detected no naked core particles in all hydrodynamically injected mice. Mutant I97L in mice exhibited pleiotropic phenotypes: (i) excessive numbers of serum HBV virions containing immature genomes, (ii) significantly reduced numbers of intracellular relaxed-circle and single-stranded DNAs, and (iii) less persistent intrahepatic and secreted HBV DNAs than wild-type HBV. These pleiotropic phenotypes were observed in both immunocompetent and immunodeficient mice. Although mutant P130T also displayed a hypermaturation phenotype in vivo, it cannot efficiently rescue the immature virion secretion of mutant I97L. Unexpectedly, the single mutant P130T exhibited in vivo a novel phenotype in prolonging the persistence of HBV genome in hepatocytes. Taken together, our studies provide a plausible rationale for HBV to regulate envelopment morphogenesis and virion secretion via genome maturity, which is likely to play an important role in the persistence of viral DNA in this mouse model. IMPORTANCE Chronic infection with human hepatitis B virus (HBV) could lead to cirrhosis and hepatoma. At present, there is no effective treatment to eradicate the virus from patients. HBV in chronic carriers does not exist as a single homogeneous population. The most frequent naturally occurring mutation in HBV core protein occurs at amino acid 97, changing an isoleucine to leucine (I97L). One dogma in the field is that only virions containing a mature genome are preferentially secreted into the medium. Here, we demonstrated that mutant I97L can secrete immature genome in mice. Although viral DNA of mutant I97L with immature genome is less persistent than wild-type HBV in time course experiments, viral DNA of mutant P130T with genome hypermaturation, surprisingly, is more persistent. Therefore, virion secretion regulated by genome maturity could influence viral persistence. It remains an open issue whether virion secretion could be a drug target for HBV therapy.


2013 ◽  
Vol 54 (5) ◽  
pp. 3350 ◽  
Author(s):  
Andrew I. Jobling ◽  
Kirstan A. Vessey ◽  
Michelle Waugh ◽  
Samuel A. Mills ◽  
Erica L. Fletcher

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e35865 ◽  
Author(s):  
Debra A. Thompson ◽  
Naheed W. Khan ◽  
Mohammad I. Othman ◽  
Bo Chang ◽  
Lin Jia ◽  
...  

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