A promising future in cancer immunotherapy: Oncolytic viruses.

Alongside the conventional methods, attention has been drawn to the use of immunotherapy-based methods for cancer treatment. Immunotherapy has developed as a therapeutic option that can be more specific with better outcomes in tumor treatment. It can boost or regulate the immune system behind the targeted virotherapy. Virotherapy is a kind of oncolytic immunotherapy that investigated broadly in cancer treatment in recent decades, due to its several advantages. According to recent advance in the field of understanding cancer cell biology and its occurrence, as well as increasing the knowledge about conditionally replicating oncolytic viruses and their destructive function in the tumor cells, nowadays, it is possible to apply this strategy in the treatment of malignancies. Relying on achievements in clinical trials of oncolytic viruses, we can certainly expect that this therapeutic perception can play a more central role in cancer treatment. In cancer treatment, combination therapy using oncolytic viruses alongside standard cancer treatment methods and other immunotherapy-based treatments can expect more promising results in the future.

Oncolytic viruses as emerging therapy against cancers including Oncovirus-induced cancers.

There are several human viruses with known potential for causing cancers including, Hepatitis B virus, Hepatitis C virus, Epstein-Barr virus, Kaposi's sarcoma herpesvirus, Human T-cell lymphotropic virus, Human papillomavirus, and Merkel cell polyomavirus. Cancer is the second leading cause of death that affects humans worldwide, especially in developing countries. Surgery, chemotherapy, and radiotherapy can cure about 60% of humans with cancer but recurrent and metastatic diseases remain a major reason for death. In recent years, understanding the molecular characteristics of cancer cells has led to the improvement of therapeutic strategies using novel emerging therapies. Oncolytic viruses with the potential of lysing cancer cells defined the field of oncolytic virology, hence becoming a biotechnology tool rather than just a cause of disease. This study mainly focused on targeting cell proliferation and death pathways in human tumor-inducing viruses by developing innovative therapies for cancer patients based on the natural oncolytic properties of reovirus. To kill tumor cells efficiently and reduce the chance of recurrence both the direct ability of reovirus infection to lyse the tumor cells and the stimulation of a potent host immune response are applied. Hence, bioengineered stem cells can be used as smart carriers to improve the efficacy of oncolytic reovirus and safety profiles.

The ins and outs of SARS-CoV-2 variants of concern (VOCs).

SARS-CoV-2, a newly emerging coronavirus that caused the COVID-19 epidemic, has been spreading quickly throughout the world. Despite immunization and some fairly effective therapeutic regimens, SARS-CoV-2 has been ravaging patients, health workers, and the economy. SARS-CoV-2 mutates and evolves to adapt to its host as a result of extreme selection pressure. As a consequence, new SARS-CoV-2 variants have emerged, some of which are classified as variants of concern (VOC) because they exhibit greater transmissibility, cause more-severe disease, are better able to escape immunity, or cause higher mortality than the original Wuhan strain. Here, we introduce these VOCs and review their characteristics, such as transmissibility, immune escape, mortality risk, and diagnostics.

MSCs loaded with oncolytic reovirus: migration and in vivo virus delivery potential for evaluating anti-cancer effect in tumor-bearing C57BL/6 mice.

BACKGROUND AND AIMS: Several oncolytic viruses applications have been approved in the clinic or in different phases of clinical trials. However, these methods have some rudimentary problems. Therefore, to enhance the delivery and quality of treatment, considering the advantage of cell carrier-based methods such as Mesenchymal Stem Cells (MSC) have been proposed. This study was designed to evaluate the performance and quality of cancer treatment based on MSCs loaded by oncolytic reovirus in the cancerous C57BL/6 mouse model. Also, we evaluated MSCs migration potency in vitro and in vivo following the oncolytic reovirus infection. METHODS: C57BL/6 mice were inoculated with TC-1 cell lines and tumors were established in the right flank. Mice were systemically treated with reovirus, MSCs-loaded with reovirus, MSCs, and PBS as a control in separated groups. Effects of infected AD-MSCs with reovirus on tumor growth and penetration in the tumor site were monitored. All groups of mice were monitored for two months in order to therapeutic and anticancer potential. After treatments, tumor size alteration and apoptosis rate, as well as cytokine release pattern was assessed. RESULTS: The results of the current study indicated that the effect of reovirus infection on AD-MSCs is not devastating the migration capacity especially in MOI 1 and 5 while intact cells remain. On the other hand, MSCs play an efficient role as a carrier to deliver oncolytic virus into the tumor site in comparison with systemic administration of reovirus alone. Apoptosis intensity relies on viral titration and passing time. Followed by systemic administration, treatment with oncolytic reovirus-infected AD-MSCs and MSCs alone had shown significant inhibition in tumor growth. Also, treatment by reovirus causes an increase in IFN-γ secretion. CONCLUSION: The results of in vitro and in vivo study confirmed the tumor-homing properties of infected AD-MSCs and the significant antitumor activity of this platform. Hence, our results showed that the cell carrier strategy using oncolytic reovirus-loaded AD-MSCs enhanced virus delivery, infiltration, and antitumor activity can be effectively applied in most cancers.

Prevalence of torque teno virus in healthy individuals and those infected with hepatitis C virus living in Yazd, Iran.

BACKGROUND: Torque teno virus (TTV) is a non-enveloped DNA virus that its role as a helper or causative agent in hepatitis is still unclear. TTV prevalence varies in different regions of the world. This study aimed to determine the prevalence of TTV in healthy individuals and those infected with hepatitis C virus (HCV) living in Yazd city, Iran. METHODS: In this case-control study, 50 healthy subjects and 68 HCV-positive individuals who referred to Yazd hospitals participated in this study. TTV DNA in serum samples were detected by nested polymerase chain reaction (PCR) using specific primers of 5΄-UTR and N22 regions. The genotypes of HCV and TTV were determined by sequencing method. RESULTS: TTV-DNA was detected in 2 out of 50 (4℅) healthy individuals and in 4 out of 68 (5.8℅) HCV-positive persons. There was not a significant correlation between the prevalence of TTV and HCV infection. The most common TTV genotypes among HCV-positive individuals were 3, 17 and 13, respectively. There was not a significant association obtained between HCV genotypes and TTV genotypes. CONCLUSION: The prevalence of TTV in Yazd province was low compared with the other areas of Iran. The prevalence of TTV in HCV infected people was not significantly higher than its rate in uninfected individuals.

Kinetics of Oncolytic Reovirus T3D Replication and Growth Pattern in Mesenchymal Stem Cells.

OBJECTIVE: Currently, application of oncolytic-virus in cancer treatment of clinical trials are growing. Oncolytic-reovirus is an attractive anti-cancer therapeutic agent for clinical testing. Many studies used mesenchymal stem cells (MSCs) as a carrier cell to enhance the delivery and quality of treatment with oncolytic-virotherapy. But, biosynthetic capacity and behavior of cells in response to viral infections are different. The infecting process of reoviruses takes from two-hours to one-week, depends on host cell and the duration of different stages of virus replication cycle. The latter includes the binding of virus particle, entry, uncoating, assembly and release of progeny-viruses. We evaluated the timing and infection cycle of reovirus type-3 strain Dearing (T3D), using one-step replication experiment by molecular and conventional methods in MSCs and L929 cell as control. MATERIALS AND METHODS: In this experimental study, L929 and adipose-derived MSCs were infected with different multiplicities of infection (MOI) of reovirus T3D. At different time points, the quantity of progeny viruses has been measured using virus titration assay and quantitative real-time polymerase chain reaction (qRT-PCR) to investigate the ability of these cells to support the reovirus replication. One-step growth cycle were examined by 50% cell culture infectious dose (CCID50) and qRT-PCR. RESULTS: The growth curve of reovirus in cells shows that MOI: 1 might be optimal for virus production compared to higher and lower MOIs. The maximum quantity of virus production using MOI: 1 was achieved at 48-hours postinfection. The infectious virus titer became stationary at 72-hours post-infection and then gradually decreased. The virus cytopathic effect was obvious in MSCs and this cells were susceptible to reovirus infection and support the virus replication. CONCLUSION: Our data highlights the timing schedule for reovirus replication, kinetics models and burst size. Further investigation is recommended to better understanding of the challenges and opportunities, for using MSCs loaded with reovirus in cancer-therapy.

Molecular Detection of Adeno-Associated Virus DNA in Cases of Spontaneous and Therapeutic Abortion.

BACKGROUND: Adeno-associated viruses (AAVs) have been found in human blood cells, cervical biopsies, and epithelial cell brushings, endometrium, and abortion material, which suggest their possible roles in the induction of miscarriage. OBJECTIVE: In this case control study, the presence of AAV DNA in placental tissue of spontaneous and therapeutic abortions was compared. METHOD: Placenta samples were evaluated for AAV DNA by hemi-nested PCR in miscarriages occurring in the first 24 weeks of pregnancy from therapeutic and spontaneous abortions. RESULTS: Eighty-one therapeutic abortions (control group) and 83 spontaneous abortions (case group) were evaluated. Sixty-two (38.2%) of 164 abortions were AAV positive, including 35 (21.6%) spontaneous abortions and 27 (16.6%) therapeutic abortions. CONCLUSION: There was no statistically significant difference between the presence of the AAV genome in spontaneous and therapeutic abortions. This observation was consistent with other studies in this area.

Molecular detection of HHV1-5, AAV and HPV in semen specimens and their impact on male fertility.

Viral infections have been considered as possible destructive factors that influence male fertility. The aim of this study was to determine the prevalence of human herpes viruses 1-5 (HHV1-5), adeno associated virus (AAV) and human papilloma virus (HPV) in semen and whether these influence semen quality. DNA extraction was performed using phenol-chloroform protocol, then three different nested-PCRs were done to detect HHV1-5, AAV and HPV DNAs in the semen samples. Of 145 samples, 66 (45.5%) were positive at least for one of the viruses. The genome detection rate of HSV1/2, VZV, EBV, HCMV, AAV and HPV were zero, 2.8%, zero, 1.4%, 27.6% and 19.3%, respectively. Of 66 positive samples for these viruses, 6 (4.1% of all samples) were positive for two viruses simultaneously. Here no association was found between variations in semen parameters related to fertility and detection of VZV, HCMV, AAV and HPV DNA in semen samples. It should be noted that the prevalence of different viruses in semen, and their relevance to male infertility, differs significantly due to the genome extraction and amplification methods or due to a real variation between study populations and geographical regions.