RNAi and miRNA in viral infections and cancers

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed

Detection of HSV-1 DNA in the Semen of Infertile Men and Evaluation of its Correlation with Semen Parameters in Iran

Background and Aims: Sexually transmitted infections (STIs) are of major concern to clinicians and researchers in the field of reproductive medicine. Many STI pathogens cause incurable and often fatal diseases, and have been transmitted through insemination procedures. The role of herpes simplex virus in male infertility has been investigated using the sensitive methods. The aim of this study was to determine the prevalence of HSV-1DNA in the semen of an asymptomatic male group with infertility problems and its association with altered semen parameters. Methods: A total of 70 semen samples from infertile men were collected in the Research and Clinical Center for Infertility Yazd, Iran. Semen analysis and diagnostic Real Time PCR using specific primers and probe for gpB gene of HSV-1, was performed for detection of HSV-1 DNA in the specimen. Results: Semen analysis showed two groups of infertile men, including male factor group and unexplained group. HSV-1 DNA was detected in 16 (22.86%) of the70 semen samples. All HSV-1positive samples had abnormal semen parameters (male factor group). Conclusion: Using a powerful molecular method, we detected a high prevalence of HSV-1 DNA in the semen of asymptomatic infertile patients. Although HSV-1 infection was not associated with motility and morphology defects of the sperms, it was related with decreased sperm count in the semen fluid

High-Risk and Low-Risk Human Papillomavirus in Esophageal Squamous Cell Carcinoma at Mazandaran, Northern Iran

Cancers are the second most common cause of nonaccidental deaths in Iran, following cardiovascular deaths. Mazandaran, near the Caspian Littoral at north of Iran have identified as a several-high incidence area for Esophageal Squamous Cell Carcinoma (ESCC) in the world. Several associated risk factors, such as dietary and cultural habits, infectious agents, nutritional deficiencies, too much use of tobacco and alcohol and infection to certain DNA tumor viruses (HPVs), including environmental and genetic factors are attributed to this disease. To explore this issue, we analyzed HPV DNA prevalence and HPV types together in relation to tumor sites a high-incidence population. Archived tissue blocks from 46, 69 and 62 upper, middle and lower third of esophagus, respectively from ESCC patients were evaluated for the presence of HPV DNA by PCR using the degenerate HPV L1 consensus primer pairs MY09/MY11. The positive specimens were evaluated by Real-time PCR to determine HPV genotypes. From the 49 HPV positive cases, of ESCC patients, 5 (23.1%), 11 (55 %) and 9 (56.3 %) of upper, middle and lower third of ESCC specimens, respectively were positive by at least one high and one low-risk HPV genotypes. In general, HPV45 and HPV11 were the most common high- risk and low-risk HPV genotypes in HPV L1 positive cases, respectively, followed by HPV6, HPV52 and HPV39. Therefore, the high prevalence of HPV DNA in different anatomical sites of ESCC patients from the Mazandaran region in North of Iran provides more evidence for a role of HPV in this cancer

Original Article Poliovirus Particles do not Form in Preinfected Cells with Reovirus

Abstract Background and Aims: Inhibition of viral growth in coinfected cells with two different viruses has been described. This phenomenon known as viral interference can occur in several virus host systems such as interference of enterovirus infection on poliovirus vaccine strains. In this study we superinfected reovirus infected HeLa cells with poliovirus to determine if poliovirus can replicate in such cells and form mature virus particles. Methods: Cells were infected first with reovirus then were reinfected with poliovirus. The amounts of viral particles were measured by electron microscopy and plaque assay titration. The amount of viral yield was also measured using the technique of real time RT-PCR for measuring the viral load in infected cells. Results: In cells infected first with reovirus and then superinfected with polio virus, only reovirus particles were produced. Virus production was determined by assaying viral titer using the plaque assay technique and electron microscopy. There was no poliovirus particles observable in the superinfected cells. The amount of poliovirus load in reovirus infected cells was also drastically reduced. Conclusion: The growth of poliovirus was inhibited in reovirus infected cells and no infectious poliovirus particles could be observed. This observation could be important to consider in poliovirus vaccination program

Prevalence of Conjunctivitis Infection by HSV-1 in Patients Referring to Hospitals Affiliated to Iran University of Medical Sciences (IUMS) in 2009

Background and Objectives: The viruses are the most common cause of eye infection. The most common viruses in conjunctivitis infection include Herpes simplex virus, Adeno virus and Entrovirus. It has been estimated that HSV1 causes 60-90% conjunctival infectionsin adults. Recurrent infection by HSV1 results in Herpes keratitis that is the most common cause for blindness in developing countries. Therefore, a prompt laboratory diagnosis is often very useful. Theaim of this study was to evaluate the prevalence of conjunctivitis infection by HSV-1 Hospital affiliated to Iran University of Medical Sciences (IUMS) in 2009.Methods: This descriptive cross-sectional study was doneon 100 tear film and eye swabs specimens from patient with symptoms of viral conjunctivitis. All samples werecollected in viral transport media (VTM) and inoculated in Vero cell line. Viral cytopatic effect was compared with control sample. HSV1 DNA wasdetected by polymerase chain reaction (PCR). Chi-square test was used to for data analysis (p<0.05).Results: Out of 100 samples under study, 2% were positive samples by cell culture, whereas in PCR9% were positive. Patients with 6-29 years old had the highest rate of HSV1 infection (13.5%) than other age groups. There was not any significant relationship between age, sex and infection.Conclusion: Herpes simplex virus infection is the major cause of conjunctivitis. Taking the recurrent infection and similarity in clinical manifestation to other infections into account, it seems necessary to have a quick and specific diagnosis of HSV for bettertreatment