راضیه سادات بنی جمالی

The Coronaviridae family includes viruses that are considered the causative agents of respiratory infections, and among human RNA viruses have the largest genome. Coronaviruses undergo elusive genetic changes through mutation during replication. A gene mutation is a permanent alteration in the nucleic acid sequence; if it occurs in large numbers, it causes changes in the biological features of a species. Fundamentally, viruses adapt to the human body during replication. Several studies have shown that most mutations do not have much effect on pathogenicity. Sequence diversity in new coronaviruses is very low. However, antigen drift has been observed among some coronaviruses. Most coronavirus mutations occur intermittently in Iran and other countries and have little effect on the pathogenicity of the virus but have increased its rate of transmission. In mutated viruses, deletion of nucleotide sequences has been observed relatively in some reading frames extensively. Studies have shown that the host protein induced mutagenesis through interaction via viral proteins. The most important mutation in SARS-CoV2 compared to the original Wuhan virus was the spike D614G mutation and the lineage of B.1.1.7, 20I/501Y.V1become the dominant and exhibit greater virus spread but did not associate with higher viral loads and morbidity. However, it may affect the effectiveness of the vaccines and mortality rate.

Oncolytic viruses (OVs) are a new approach in treatment of cancer. Antitumor efficacy of OVs were limited due to insufficient and non-specific viral delivery to tumor sites. To overcome this issue, mesenchymal stem cells (MSCs) were used for their ability to specifically homing into tumors. The main aim of this study was to use MSCs as carriers and investigate the effect of oncolytic reovirus infection in MSCs, induction of apoptosis, nitric oxide (NO) secretion and their effects for selectively killing tumor cells, to use in future. MSCs isolated from mice adipose tissue and confirmed. Then, the ability of the virus to infect MSCs and the effect of reovirus infection in induction of apoptosis and NO secretion in MSCs were evaluated. The results demonstrate that reovirus could replicate on MSCs. The finding indicated that the NO production significantly was higher at 72 h post infection with different MOI in comparison to the control cells. Also, reovirus induced high level of apoptosis in the MSCs at 48 h post infection compared with the control cells. Based on observed results, reovirus increased the secretion of iNOS (inducible nitric oxide) in the infected MSCs at 48 h post infection; therefore, high amounts of NO and reovirus replication were found to trigger apoptosis at 48 h post infection. Therefore, by optimizing the replication time of virus in the MSCs, specific viral delivery to tumor sites are available and causes cancer cells’ death.