ABSTRACT
Human adenovirus (HAdV) species B can cause severe acute respiratory diseases. However, the researches to combat this infection have been hampered by the lack of an animal model permissive to the virus. Here, we report in vitro and in vivo HAdV species B infections of tree shrews, the closest relative of primates. HAdV-3, -7, -14, and -55 efficiently replicated in primary cell cultures. After intranasal inoculation of tree shrews with HAdV-55, the viral replication in the oropharyngeal region remained high until day 5 post-infection and was still detected until day 12. HAdV-55 in the lung or turbinate bone tissues reached the highest levels between days 3 and 5 post-infection, which indicated viral replication in the upper and lower respiratory tracts. HAdV-55 infection caused severe interstitial pneumonia in the animal. IL-8, IL-10, IL-17A, and IFN-γ expression in the peripheral blood mononuclear cells from infected animals was up-regulated. The pre-vaccination with HAdV-55 cleared the virus faster in the respiratory tract, mitigated lung pathological changes. Finally, HAdV-55 infection was propagated among tree shrews. Our study demonstrated that the tree shrew is a permissive animal model for HAdV species B infection and may serve as a valuable platform for testing multiple anti-viral treatments.
Subject(s)
Adenoviruses, Human/physiology , Cytokines/metabolism , Lung Diseases, Interstitial/virology , Tupaiidae/virology , Animals , Cells, Cultured , Disease Models, Animal , Hep G2 Cells , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-17/metabolism , Interleukin-8/metabolism , Lung Diseases, Interstitial/immunology , Male , Oropharynx/virology , Primary Cell Culture , Up-Regulation , Virus ReplicationABSTRACT
The oncogenic role of Wilms' tumor 1 (WT1) which is regarded as a promising target antigen for cancer immunotherapy has been demonstrated in many types of cancer, but the relationship between expression of WT1 and the prognosis value in gynecological cancer reminds unclear.We performed a meta-analysis with thirteen published studies including 2205 patients searched from PubMed, EMBASE, Web of Science, and Google Scholar, whose results are expressed by overall survival (OS) or disease-specific survival (DSS) or disease-free survival or relapse/recurrence-free survival (RFS) or progression-free survival (PFS) in patients with gynecological cancer. The hazard ratio (HR) with its 95% confidence interval (CI) were calculated to investigate prognostic of WT1 expression in patients with gynecological cancer.Finally, the overexpression of WT1 was borderlinely associated with poor OS (metaHRâ=â1.51, 95% CIâ=â0.98-2.31) in univariate model. We found a significant association with poor DSS (metaHRâ=â1.61, 95% CIâ=â1.24-2.08) and DFS/RFS/PFS (metaHRâ=â2.06, 95% CIâ=â1.22-3.46). The subgroup analyses revealed that the expression of WT1 predicted the poor DSS (metaHRâ=â1.82, 95% CIâ=â1.42-2.73), and DFS/RFS/PFS (metaHRâ=â2.51, 95% CIâ=â1.81-3.48) in patients with ovarian cancer. In summary, WT1 overexpression indicates a poor prognosis in patients with some gynecological tumors, but more studies are needed to confirm these findings.
