Evaluation of the Expression Pattern of 4 microRNAs and their Correlation with Cellular/viral Factors in PBMCs of Long Term Non-progressors and HIV Infected Naïve Individuals.

BACKGROUND: Long-term non-progressors (LTNPs) are small subsets of HIV-infected subjects that can control HIV-1 replication for several years without receiving ART. The exact mechanism of HIV-1 suppression has not yet been completely elucidated. Although the modulatory role of microRNAs (miRNAs) in HIV-1 replication has been reported, their importance in LTNPs is unclear. OBJECTIVE: The aim of this cross-sectional study was to assess the expression pattern of miR-27b, -29, -150, and -221, as well as their relationship with CD4+ T-cell count, HIV-1 viral load, and nef gene expression in peripheral blood mononuclear cells (PBMCs) of untreated viremic patients and in LTNPs. METHODS: MiRNAs expression levels were evaluated with real-time PCR assay using RNA isolated from PBMCs of LTNPs, HIV-1 infected naive patients, and healthy people. Moreover, CD4 T-cell count, HIV viral load, and nef gene expression were assessed. RESULTS: The expression level of all miRNAs significantly decreased in the HIV-1 patient group compared to the control group, while the expression pattern of miRNAs in the LNTPs group was similar to that in the healthy subject group. In addition, there were significant correlations between some miRNA expression with viral load, CD4+ T-cell count, and nef gene expression. CONCLUSION: The significant similarity and difference of the miRNA expression pattern between LNTPs and healthy individuals as well as between elite controllers and HIV-infected patients, respectively, showed that these miRNAs could be used as diagnostic biomarkers. Further, positive and negative correlations between miRNAs expression and viral/cellular factors could justify the role of these miRNAs in HIV-1 disease monitoring.

Circular RNAs: New Epigenetic Signatures in Viral Infections.

Covalent closed circular RNAs (circRNAs) can act as a bridge between non-coding RNAs and coding messenger RNAs. CircRNAs are generated by a back-splicing mechanism during post-transcriptional processing and are abundantly expressed in eukaryotic cells. CircRNAs can act via the modulation of RNA transcription and protein production, and by the sponging of microRNAs (miRNAs). CircRNAs are now thought to be involved in many different biological and pathological processes. Some studies have suggested that the expression of host circRNAs is dysregulated in several types of virus-infected cells, compared to control cells. It is highly likely that viruses can use these molecules for their own purposes. In addition, some viral genes are able to produce viral circRNAs (VcircRNA) by a back-splicing mechanism. However, the viral genes that encode VcircRNAs, and their functions, are poorly studied. In this review, we highlight some new findings about the interaction of host circRNAs and viral infection. Moreover, the potential of VcircRNAs derived from the virus itself, to act as biomarkers and therapeutic targets is summarized.

Occult HCV and occult HBV coinfection in Iranian human immunodeficiency virus-infected individuals.

The presence of hepatitis C virus (HCV) genome in liver biopsy or peripheral blood mononuclear cell (PBMC) specimens in the absence of detectable HCV-RNA in plasma of the people with or without anti-HCV antibodies has defined as occult HCV infection (OCI), whereas occult hepatitis B virus infection (OBI) is detection of hepatitis B virus (HBV) genome in the absence of traceable hepatitis B surface antigen in the plasma samples of patients. The purpose of this study is to determine the presence of OBI and OCI in human immunodeficiency virus (HIV)-infected individuals. In this cross-sectional research, 190 Iranian HIV-infected individuals were enrolled from September 2015 to February 2019. All participants were tested regarding various serological markers for HCV and HBV infections. Viral RNA and DNA were extracted from plasma and PBMC specimens, and the presence of HCV-RNA in plasma and PBMC samples was tested using reverse transcriptase-nested polymerase chain reaction (PCR), HBV viral load was determined in plasma samples using COBAS TaqMan 48 Kit, and also the presence of the HBV-DNA in PBMC samples was tested by real-time PCR. In this study, the prevalence of OBI and OCI in HIV-infected individuals was 3.1% and 11.4%, respectively. The genotypes of HCV in the patients with OCI were as follows: 57.1% were infected with subtype 3a, 35.7% were infected with subtype 1a, and 7.1% was infected with subtype 1b. It is noteworthy that in this study, two patients (1.1%) had OCI/OBI coinfections. The present study revealed that 1.1% of Iranian HIV-infected individuals had OBI and OCI at the same time. Therefore, it seems that designing prospective surveys to determine the presence of this coinfection in HIV-infected individuals is informative.

The role of miR-146a in viral infection.

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.

Evaluation of CCR5-Δ32 mutation among individuals with high risk behaviors, neonates born to HIV-1 infected mothers, HIV-1 infected individuals, and healthy people in an Iranian population.

One of the important genetic factors related to resistance to HIV-1 infection is the presence of the C-C chemokine receptor type 5 delta 32 (CCR5-Δ32) homozygous genotype (Δ32/Δ32). The aim of this study was to evaluate the CCR5-Δ32 mutation among individuals with high-risk behaviors, neonates born to HIV-1-infected mothers in the prevention of mother-to-child transmission (PMTCT) project, HIV-1-infected individuals, and healthy people. The frequency of the CCR5-Δ32 genotype was assessed in a cross-sectional survey carried out from March 2014 to March 2019 among four different groups of the Iranian population. Genomic DNA was extracted from peripheral blood mononuclear cells of 140 Iranian healthy people, 84 neonates born to HIV-1-infected mothers in the PMTCT project, 71 people with high-risk behaviors, and 76 HIV-1-infected individuals. The polymerase chain reaction method was used for the amplification of the CCR5 gene. The CCR5-Δ32 heterozygous deletion was detected in five (6.6%) HIV-1-infected individuals, four (4.7%) neonates born to HIV-1 positive mothers, two (1.4%) healthy people, and also three (4.2%) people with high-risk behaviors whereas the CCR5-Δ32 homozygous deletion was absent in all the groups (Fisher's exact test, P = .0242). The allele of CCR5-Δ32 homozygous was not detected in the four study groups, and no significant difference was seen in the frequency of the CCR5Δ32 heterozygous allele between HIV seropositive and seronegative individuals. Therefore, it seems that this allele alone cannot explain the natural resistance to HIV-1 infection and probably several mechanisms are responsible for these processes and it should be further investigated.