Prevalence of Naturally Occurring Resistance Associated Substitutions in NS3/4AProtease Inhibitors in Iranian HCV/HIV Infected Patients.

BACKGROUND: Hepatitis C virus (HCV) acts in the host as a complicated mixture of related variants with the potency to genetically escape host immune responses. Direct acting antivirals (DAAs) have been approved for HCV treatment with shorter duration, better cure rates and lower side effects. However, naturally occurring resistance associated substitutions (RASs) create some obstacles to this antiviral therapy success. OBJECTIVE: In this study, we aimed at the determination of the naturally occurring NS3/4A RASs in HCV/human immunodeficiency virus (HIV)infected patients. METHODS: A total of 120 DAA-naïve HCV-HIV co-infected patients were included. HCV NS3/4Agenome region was amplified with PCR and mutation analysis was performed by Sanger sequencing technique. The amino acid sequence diversity of the region was analyzed using geno2pheno HCV. RESULTS: Phylogenetic analysis showed that 73 cases were infected by 3a and 47 subjects by subtype1a. The overall RASs among studied subjects were observed in 6 (5%) individuals from 120 studied cases who were infected with HCV 1a. V36M/L, Q80L, S122G/L, R155T/G, A156S, D168Y/N and S174A/N/T mutations were detected in this study. CONCLUSION: Although the prevalence of RASs was totally low in this study, the presence of several cases of double and triple mutants among this population suggests prior evaluation of protease inhibitors related mutations before initiation of standard treatment and also an investigation on a large population could be of high value.

Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development.

INTRODUCTION: The sexually transmitted infections (STIs) caused by viruses including human T cell leukemia virus type-1 (HTLV-1), human immunodeficiency virus-1 (HIV-1), human simplex virus-2 (HSV-2), hepatitis C virus (HCV), hepatitis B virus (HBV), and human papillomavirus (HPV) are major public health issues. These infections can cause cancer or result in long-term health problems. Due to high prevalence of STIs, a safe and effective vaccine is required to overcome these fatal viruses. AREAS COVERED: This review includes a comprehensive overview of the literatures relevant to vaccine development against the sexually transmitted viruses (STVs) using PubMed and Sciencedirect electronic search engines. Herein, we discuss the efforts directed toward development of effective vaccines using different laboratory animal models including mice, guinea pig or non-human primates in preclinical trials, and human in clinical trials with different phases. EXPERT OPINION: There is no effective FDA approved vaccine against the sexually transmitted viruses (STVs) except for HBV and HPV as prophylactic vaccines. Many attempts are underway to develop vaccines against these viruses. There are several approaches for improving prophylactic or therapeutic vaccines such as heterologous prime/boost immunization, delivery system, administration route, adjuvants, etc. In this line, further studies can be helpful for understanding the immunobiology of STVs in human. Moreover, development of more relevant animal models is a worthy goal to induce effective immune responses in humans.

Pharmaceutical Approaches for Treatment of Hepatitis C virus.

Many studies have been performed to develop an antiviral therapy against the hepatitis C virus (HCV) infections. The usual treatment for HCV infection is a combination of PEGylated interferon and ribavirin which offer restricted efficiency and major side effects. Thus, recent development in molecular biology of HCV and its life cycle led to the design of many drugs that target viral proteins and host factors required for viral replication. These drugs were named as direct-acting antivirals (DAAs) that were specifically designed for inhibition of viral life cycle, promising tolerability, short duration of treatment, higher barrier to resistance, and fewer drug interactions. The use of DAAs for the treatment of HCV infection resulted in high virological cure rates in patients. However, the use of combined DAA regimens may present drug interactions especially in patients under treatment for other co-morbidities. On the other hand, drug resistance against virus infection determines the success of long-term therapy. High genetic diversity among HCV virions due to error-prone polymerase activity led to the reduced susceptibility to DAA-therapy. Therefore, preclinical and clinical analysis of HCV resistance to novel drugs is needed. In this review, we describe pharmaceutical approaches for HCV treatment, structural and functional properties of DAAs, the principles of HCV drug-drug interaction, and finally HCV resistance to DAAs.

Comparing the Frequency of CD4+T Cells in Recurrent Spontaneous Abortion Women with and without Anti-thyroid Peroxidase (TPO).

Thyroid autoimmunity, being recognized by the presence of auto-antibodies against thyroid peroxidase (TPO) and thyroglobulin, has known to be associated with increased risk of recurrent spontaneous abortion (RSA), even in euthyroid subjects. There was no robust evidence regarding T cell deviations in anti-TPO positive RSA patients. The aim of this study was to investigate if the numbers of different CD4+T  subsets were different in women who experienced RSA and have an anti-TPO antibody from those without autoantibody and normal fertile women or not. In this study, peripheral blood samples were obtained from three groups of women (age: 20-35 years) including RSA anti-TPO positive (n=17), RSA anti-TPO negative (n=27), and fertile (n=29) groups. The frequency of T helper (Th) 1, Th2, Th17, and regulatory T cells (Tregs) and also, the proportions of Th1/Th2 and Th17/Treg were measured by flow cytometry and compared between groups in different menstrual phases. The findings indicated elevated levels of Th1 in anti-TPO+ RSA in comparison with those without anti-TPO (p-value: 0.004), exclusively in the luteal phase. Other T cell subsets were different only between RSA and control groups. Also, the Th1/Th2 and Th17/Treg ratios were increased in both RSA groups compared to fertile women. The only subset of CD4+ T cell different between RSA groups (i.e. with and without anti-TPO) was Th1 cells. Other CD4+ T cells' deviations including Th2, Th17, and Treg cells could be related to the presence of abortion, regardless of the underlying thyroid autoimmunity state.

Anti-viral Effects of Superpositively Charged Mutant of Green Fluorescent Protein.

BACKGROUND: Supercharged GFP proteins were known as effective carriers for delivery of macromolecules into eukaryotic cells as well as fluorescent fusion tags for in vitro and in vivo detection. OBJECTIVE: Herein, anti-viral effects of +36 GFP and its anti-tumor effects were studied in vitro and in vivo, respectively. METHODS: We evaluated anti-HIV, anti-HSV, and anti-HCV effects of +36 GFP in vitro using ELISA, and real time PCR as common techniques for their detection, respectively. Moreover, we assessed the role of +36 GFP for eliciting HPV-related anti-tumor effects in mice due to the lack of HPV replication in vitro. RESULTS: Our data showed that +36 GFP efficiently enter the cells and augment the transfection rate of HPV16E7 antigen, as well. Furthermore, +36 GFP significantly reduced HCV, HIV and HSV replication up to 75%, 49% and 43% in HCV-infected Huh7.5 cells, HIV-infected Hela cells and HSV-infected Vero cells, respectively. On the other hand, mice immunization with +36 GFP complexed with HPV16 E7 antigen (+36GFP + E7) or fused to HPV16 E7 antigen (+36GFP-E7) elicited a higher Th1 cellular immune response with the predominant IgG2a, IgG2b, IFN-γ and Granzyme B levels than those induced by other groups. These regimens protected mice against TC- 1 tumor challenge (~ 67%) compared to E7 protein alone (~ 33%). These data suggested that +36 GFP can act as an anti-viral agent at certain dose due to its high efficiency in cell penetration in vitro and in vivo. CONCLUSION: Generally, +36 GFP targets viral replication in vitro as well as helps to suppress the growth of HPV-related tumors in vivo.