The vaccinia virus E6R gene (VACVWR062) is conserved in all members of the poxvirus family and encodes a protein associated with the mature virion. We confirmed this association and provided evidence for an internal location. An inducible mutant that conditionally expresses E6 was constructed. In the absence of inducer, plaque formation and virus production were severely inhibited in several cell lines, whereas some replication occurred in others. This difference could be due to variation in the stringency of repression, since we could not isolate a stable deletion mutant even in the more "permissive" cells. Under non-permissive conditions, viral late proteins were synthesized but processing of core proteins was inefficient, indicative of an assembly block. Transmission electron microscopy of sections of cells infected with the mutant in the absence of inducer revealed morphogenetic defects with crescents and empty immature virions adjacent to dense inclusions of viroplasm. Mature virions were infrequent and cores appeared to have lucent centers.
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http://dx.doi.org/10.1016/j.virol.2009.01.009 | DOI Listing |
Exp Parasitol
January 2025
Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea; Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address:
Toxoplasmosis is a parasitic disease affecting a significant portion of the global population, whose etiology can be attributed to the protozoan organism Toxoplasma gondii. Despite its public health importance, an efficacious vaccine to prevent human toxoplasmosis remains unavailable. To this end, we designed an experimental toxoplasmosis vaccine using recombinant vaccinia virus vectors (rVacv) expressing the T.
View Article and Find Full Text PDFJ Immunother Cancer
December 2024
Department of Clinical Laboratory, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China
Objective: Targeting CD47 for cancer immunotherapy has been studied in many clinical trials for the treatment of patients with advanced tumors. However, this therapeutic approach is often hampered by on-target side effects, physical barriers, and immunosuppressive tumor microenvironment (TME).
Methods: To improve therapeutic efficacy while minimizing toxicities, we engineered an oncolytic vaccinia virus (OVV) encoding an anti-CD47 nanobody (OVV-αCD47nb).
JYNNEOS, a third-generation smallpox vaccine, is integral to monkeypox virus (MPXV) control efforts, but the durability of this modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine's effectiveness is undefined. We optimized and used a plaque reduction neutralization test (PRNT) with authentic clade IIa MPXV and vaccinia virus to assess antibody responses over 12 months in 8 donors vaccinated with 2 doses of JYNNEOS. One donor previously received the ACAM2000 vaccine; 7 donors were smallpox vaccine-naive.
View Article and Find Full Text PDFClin Cancer Res
January 2025
University of Leeds, Leeds, United Kingdom.
Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.
Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.
CPT Pharmacometrics Syst Pharmacol
January 2025
Astellas Pharma Inc., Northbrook, Illinois, USA.
The antitumor efficacy of an intratumoral injection of a genetically engineered oncolytic vaccinia virus carrying human IL-7 and murine IL-12 genes (hIL-7/mIL-12-VV) was demonstrated in CT26.WT-bearing mice. In the CT26.
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