-
Description: Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), remains a major medical problem. HBV has a high propensity for progressing to chronicity and can result in severe liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma. CHB patients frequently present with viral coinfection, including HIV and hepatitis delta virus. About 10% of chronic HIV carriers are also persistently infected with HBV which can result in more exacerbated liver disease. Mechanistic studies of HBV-induced immune responses and pathogenesis, which could be significantly influenced by HIV infection, have been hampered by the scarcity of immunocompetent animal models. Here, we demonstrate that humanized mice dually engrafted with components of a human immune system and a human liver supported HBV infection, which was partially controlled by human immune cells, as evidenced by lower levels of serum viremia and HBV replication intermediates in the liver. HBV infection resulted in priming and expansion of human HLA-restricted CD8+ T cells, which acquired an activated phenotype. Notably, our dually humanized mice support persistent coinfections with HBV and HIV which opens opportunities for analyzing immune dysregulation during HBV and HIV coinfection and preclinical testing of novel immunotherapeutics.
Show More
# | Filename | Filesize |
---|---|---|
1 | README.txt | 6.3 KB |
2 | Figure 1 - CD45 human ___(13).xlsx | 10.7 KB |
3 | Figure 1 - hCD45_ cells in blood ___(12).xlsx | 9.82 KB |
4 | Figure 2 - HBV DNA _copies per mg tissue_(9).xlsx | 10.3 KB |
5 | Figure 2 - HBV DNA in serum _GE per ml_(8).xlsx | 10.7 KB |
6 | Figure 2 - HBV cccDNA _copies per mg tissue_(10).xlsx | 10.2 KB |
7 | Figure 2 - HBV pc.pgRNA _copies per mg tissue_(7).xlsx | 10.2 KB |
8 | Figure 2 - HBsAg _GE per ml_(11).xlsx | 10.8 KB |
9 | Figure 3 - HBV core tetramer-positive CD8_ T subpopulatio... | 10.5 KB |
10 | Figure 3 - HBV core tetramer-positive CD8_ T subpopulatio... | 10.5 KB |
11 | Figure 5 - HBV DNA copies _GE per mg tissue_(4).xlsx | 9.38 KB |
12 | Figure 5 - HBV pc.pgRNA _GE per mg tissue_(3).xlsx | 9.35 KB |
13 | Figure 5 - HBsAg _IU per ml_(14).xlsx | 9.81 KB |
14 | Figure 6 - HBV DNA in plasma _copies per ml_(2).xlsx | 9.76 KB |
15 | Figure 6 - HIV RNA in plasma _copies per ml_(1).xlsx | 9.74 KB |
16 | Figure 6 - Hepatic HBV pc.pgRNA fold change.xlsx | 9.6 KB |
17 | Figure 6 - Hepatic HIV RNA fold change.xlsx | 9.61 KB |
18 | Figure 7 - hAPO3G fold change.xlsx | 10.4 KB |
19 | Figure 7 - hARG1 fold change.xlsx | 10.4 KB |
20 | Figure 7 - hCD163 fold change.xlsx | 10.4 KB |
21 | Figure 7 - hIFITM3 fold change.xlsx | 10.5 KB |
22 | Figure 7 - hIFN-b fold change.xlsx | 10.4 KB |
23 | Figure 7 - hISG-15 fold change.xlsx | 10.4 KB |
24 | Figure 7 - hMX-1 fold change.xlsx | 10.4 KB |
25 | Figure 7 - hOAS1 fold change.xlsx | 10.4 KB |
26 | Figure 7 - hTGF-b fold change.xlsx | 10.5 KB |
27 | Figure 7 - hTIMP-1 fold change.xlsx | 10.5 KB |
28 | renamed_files.txt | 2.18 KB |