The landscape of persistent human DNA viruses in femoral bone
FORENSIC SCIENCE INTERNATIONAL-GENETICS
Authors: Toppinen, Mari; Pratas, Diogo; Vaisanen, Elina; Soderlund-Venermo, Maria; Hedman, Klaus; Perdomo, Maria F.; Sajantila, Antti
Abstract
The imprints left by persistent DNA viruses in the tissues can testify to the changes driving virus evolution as well as provide clues on the provenance of modern and ancient humans. However, the history hidden in skeletal remains is practically unknown, as only parvovirus B19 and hepatitis B virus DNA have been detected in hard tissues so far. Here, we investigated the DNA prevalences of 38 viruses in femoral bone of recently deceased individuals. To this end, we used quantitative PCRs and a custom viral targeted enrichment followed by next generation sequencing. The data was analyzed with a tailor-made bioinformatics pipeline. Our findings revealed bone to be a much richer source of persistent DNA viruses than earlier perceived, discovering ten additional ones, including several members of the herpesand polyomavirus families, as well as human papillomavirus 31 and torque teno virus. Remarkably, many of the viruses found have oncogenic potential and/or may reactivate in the elderly and immunosuppressed individuals. Thus, their persistence warrants careful evaluation of their clinical significance and impact on bone biology. Our findings open new frontiers for the study of virus evolution from ancient relics as well as provide new tools for the investigation of human skeletal remains in forensic and archaeological contexts.
Oncolytic Virotherapy for Malignant Tumor: Current Clinical Status
CURRENT PHARMACEUTICAL DESIGN
Authors: Zhang, Yuhui; Liu, Zhuoming
Abstract
Oncolytic viruses, as novel biological anti-tumor agents, provide anti-tumor therapeutic effects by different mechanisms including directly selective tumor cell lysis and secondary systemic anti-tumor immune responses. Some wide-type and genetically engineered oncolytic viruses have been applied in clinical trials. Among them, T-Vec has a significant therapeutic effect on melanoma patients and received the approval of the US Food and Drug Administration (FDA) as the first oncolytic virus to treat cancer in the US. However, the mechanisms of virus interaction with tumor and immune systems have not been clearly elucidated and there are still no "gold standards" for instructions of virotherapy in clinical trials. This Review collected the recent clinical trials data from 2005 to summarize the basic oncolytic viruses biology, describe the application in recent clinical trials, and discuss the challenges in the application of oncolytic viruses in clinical trials.