Virus Disease Progression Research Articles

Mycobiome profiling of nasopharyngeal region of SARS-CoV-2 infected individuals

The present cross-sectional study aims to understand the fungal community composition of the nasopharyngeal region of SARS-CoV-2 infected individuals and how the infection influences the mycobiome therein. The infection significantly (p < 0.05) influenced the alpha diversity. Interestingly, a higher abundance of Cladosporium and Alternaria was noted in the infected individuals and inter-individual variation in mycobiome composition was well supported by beta dispersion analysis (p < 0.05). Moreover, decrease in Aspergillus abundance was observed in infected patients across the four age groups. This study provides insight into the alteration in mycobiome during the viral disease progression and demands continuous investigation to monitor fungal infections.

Dynamic changes in virus-induced volatiles in cotton modulate the orientation and oviposition behavior of the whitefly Bemisia tabaci.

Manipulation of insect vector behavior by virus-induced plant volatiles is well known. But how the viral disease progression alters the plant volatiles and its effect on vector behavior remains less explored. Our studies tracked changes in volatile profile in progressive infection stages of cotton leaf curl virus (CLCuV) infected plants and their effect on B. tabaci behavior. Significant differences in virus titers were noticed between progressive infection stages showing distinct symptoms. Whiteflies initially settled on CLCuV infected plants, but their preference was shifted to healthy plants over time. GC-MS analysis revealed subtle quantitative/qualitative changes in volatile organic compounds (VOCs) between the healthy and selected CLCuV infection stages. VOCs such as hexanal, (E)-2-hexen-1-ol, (+)-α-pinene, (−)-β-pinene, (Z)-3-hexen-1-ol, (+)-sylvestrene, and (1S,2E,6E, 10R)-3,7,11,11-tetramethylbicycloundeca-2,6-diene (Bicyclogermacrene) were associated with the infection stage showing upward curling of leaves; (E)-2-hexen-1-ol, β-myrcene, β-ocimene, and copaene were associated with the infection stage showing downward curling. Validation studies with eight synthetic VOCs indicated that γ-terpinene elicited attraction to B. tabaci (Olfactometric Preference Index (OPI) = 1.65), while β-ocimene exhibited strong repellence (OPI = 0.64) and oviposition reduction (66.01%–92.55%). Our studies have demonstrated that progression of CLCuV disease in cotton was associated with dynamic changes in volatile profile which influences the behavioural responses of whitefly, B.tabaci. Results have shown that VOCs such as (+)-α-pinene, (−)-β-pinene γ-Terpinene, α-guaiene; 4- hydroxy- 4 methyl-2- pentanone and β-ocimene emitted from Begomovirus infected plants could be the driving force for early attraction and later repellence/oviposition deterrence of B. tabaci on virus-infected plants. The findings of this study offer scope for the management of whitefly, B. tabaci through semiochemicals.

Altered HIV-1 Viral Copy Number and Gene Expression Profiles of Peripheral (CEM CCR5+) and Mucosal (A3R5.7) T Cell Lines Co-Infected with HSV-2 In Vitro.

Co-infecting pathogens have been speculated to influence Human Immunodeficiency Virus (HIV) disease progression. Herpes Simplex Virus Type-2 (HSV-2), another sexually transmitted pathogen, is commonly observed in individuals with HIV-1. Some clinical studies have observed an increase in HIV-1 viral copy number in HSV-2 co-infected individuals. In vitro studies have also demonstrated an increase in the expression of HIV-1 co-receptors on immune cells infected with HSV-2. Although both the viruses show distinctive persistent infection, the influence of HSV-2 on HIV-1 is poorly understood. Here we present a comparative analysis of primary CD4+ T-cells and four different T-cell lines (PM-1, CEM CCR5+, MOLT4 CCR5+, and A3R5.7) to assess the influence of HSV-2 co-infection on HIV-1 replication in vitro. Cell lines indicating significant changes in HIV-1 viral copy number [CEM CCR5+ (0.61 Log10), A3R5.7 (0.78 Log10)] were further evaluated for the infectivity of HIV-1 virions and the changes in gene expression profiles of HSV-2/HIV-1 co-infected and mono-infected cells, which were further confirmed by qPCR. Significant changes in NUP, MED, and VPS mRNA expression were observed in the gene expression profiles in co-infected CEM CCR5+ and A3R5.7 cells. In both cell lines, it was observed that the WNT signaling, PI3 kinase, apoptosis, and T-cell activation pathways were negatively affected in co-infected cells. The data suggest that HSV-2 infection of T-cells may influence the expression of genes that have been previously shown to affect HIV-1 replication in vitro. This idea needs to be explored further to identify anti-viral targets for HSV-2 and HIV-1.

Plant-virus-abiotic stress interactions: A complex interplay

Under field conditions, plants are subjected to a wide array of biotic and abiotic stresses. These are detrimental to the survival of plants and adversely affects global crop productivity. Changing climate has led to elevated temperatures and unpredicted whether patterns across the world leading to suboptimal crop performance. This is coupled by the emergence of novel pathogen strains which are resistant to anti-pathogenic agents. The situation is even worse in case of viruses where antiviral agents for controlling viral diseases in plants is lacking. The explosion of international trade has helped in the sharing of surplus resources from one location to the other and benefitted the economy of most countries however, this has also resulted in the spread of viruses and other pathogens. Recent years have seen a paradigm shift in the research methodology with combined stress gaining major attention instead of solitary stress. Viruses influence a plant’s response to various abiotic stresses, similarly, abiotic stress imposition has a great effect on viral disease progression. The recent developments associated with plant-virus-abiotic stress interactions along with the way forward to tackle such stresses has been discussed in the present review. • The interaction between plant, virus and abiotic stresses is less understood. • Viruses tend to show enhanced virulence during higher temperatures. • Plants infected with certain viruses are more tolerant to drought and cold stress. • The global spread of plant viruses along with the rapid climate change demands robust research in this area.

Role of Microbiota in Viral Infections and Pathological Progression.

Viral infections are influenced by various microorganisms in the environment surrounding the target tissue, and the correlation between the type and balance of commensal microbiota is the key to establishment of the infection and pathogenicity. Some commensal microorganisms are known to resist or promote viral infection, while others are involved in pathogenicity. It is also becoming evident that the profile of the commensal microbiota under normal conditions influences the progression of viral diseases. Thus, to understand the pathogenesis underlying viral infections, it is important to elucidate the interactions among viruses, target tissues, and the surrounding environment, including the commensal microbiota, which should have different relationships with each virus. In this review, we outline the role of microorganisms in viral infections. Particularly, we focus on gaining an in-depth understanding of the correlations among viral infections, target tissues, and the surrounding environment, including the commensal microbiota and the gut virome, and discussing the impact of changes in the microbiota (dysbiosis) on the pathological progression of viral infections.

A Systematic Molecular Epidemiology Screen Reveals Numerous Human Immunodeficiency Virus (HIV) Type 1 Superinfections in the Swiss HIV Cohort Study.

Studying human immunodeficiency virus type 1 (HIV-1) superinfection is important to understand virus transmission, disease progression, and vaccine design. But detection remains challenging, with low sampling frequencies and insufficient longitudinal samples. Using the Swiss HIV Cohort Study (SHCS), we developed a molecular epidemiology screening for superinfections. A phylogeny built from 22 243 HIV-1 partial polymerase sequences was used to identify potential superinfections among 4575 SHCS participants with longitudinal sequences. A subset of potential superinfections was tested by near-full-length viral genome sequencing (NFVGS) of biobanked plasma samples. Based on phylogenetic and distance criteria, 325 potential HIV-1 superinfections were identified and categorized by their likelihood of being detected as superinfections due to sample misidentification. NFVGS was performed for 128 potential superinfections; of these, 52 were confirmed by NFVGS, 15 were not confirmed, and for 61 sampling did not allow confirming or rejecting superinfection because the sequenced samples did not include the relevant time points causing the superinfection signal in the original screen. Thus, NFVGS could support 52 of 67 adequately sampled potential superinfections. This cohort-based molecular approach identified, to our knowledge, the largest population of confirmed superinfections, showing that, while rare with a prevalence of 1%-7%, superinfections are not negligible events.

Novel factors to predict respiratory viral disease progression in allogeneic hematopoietic cell transplant recipients.

We assessed novel factors and the immunodeficiency scoring index (ISI) to predict progression to lower respiratory tract infection (LRTI) among hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. We retrospectively analyzed the first respiratory virus detected by multiplex PCR in allogeneic HCT recipients (4/2008–9/2018). We used Cox proportional hazards models to examine factors for progression to LRTI within 90 days among patients presenting with URTI. A total of 1027 patients (216 children and 811 adults) presented with URTI only. Among these, 189 (18%) progressed to LRTI (median: 12 days). Multivariable models demonstrated a history of >1 transplant, age ≥40 years, time post-HCT (≤30 days), systemic steroids, hypoalbuminemia, hyperglycemia, cytopenia, and high ISI (scores 7–12) were associated with an increased risk of progression to LRTI. Respiratory syncytial virus and human metapneumovirus showed the highest progression risk. Patients with ≥3 independent risk factors or high ISI scores were highly likely to progress to LRTI. We identified novel risk factors for progression to LRTI, including history of multiple transplants and hyperglycemia, suggesting an intervention opportunity with glycemic control. ISI and number of risk factors appear to predict disease progression across several viruses.

Higher Risk of Mortality and Virologic Failure in HIV-Infected Patients With High Viral Load at Antiretroviral Therapy Initiation: An Observational Cohort Study in Chongqing, China.

BackgroundViral load (VL) is a strong predictor of human immunodeficiency virus (HIV) disease progression. The aim of this study was to evaluate the effect of high baseline VL on antiretroviral therapy (ART) outcomes among HIV-infected patients.MethodsThis retrospective study observed HIV-infected patients who had baseline VL test at ART initiation between 2015 and 2019 in Chongqing, China. Cox proportional hazards regression and logistic regression models were used to evaluate the effects of baseline VL on Acquired immunodeficiency syndrome (AIDS)-related mortality and virologic failure, respectively.ResultsThe cohort included 7,176 HIV-infected patients, of whom 38.7% had a baseline VL ≥ 100,000 copies/mL. Of the patients who died during follow-up, 58.9% had a baseline VL ≥ 100,000 copies/mL. Compared with a baseline VL < 10,000 copies/mL, ART initiation at VL ≥ 100,000 copies/mL was significantly associated with the AIDS-related death (adjusted hazard ratio, AHR = 1.4) and virologic failure (adjusted odds ratio, AOR = 2.4). Compared with patients with a baseline VL < 10,000 copies/mL, patients on the recommended first-line regimen with a VL ≥ 100,000 copies/mL at ART initiaition had higher mortality rate (5.1 vs. 1.7 per 100 person-years), but there was no significant difference in the mortality accoding to the initial VL level among patients on second-line ART (2.8 vs. 2.7 per 100 person-years). ART initiation ≤ 30 days after HIV diagnosis was associated with a lower risk of AIDS-related death (AHR = 0.6).ConclusionsART initiation with VL ≥ 100,000 copies/mL was associated with a significantly greater risk of mortality and virologic failure. Optimizing the ART regimen and initiating ART early may help to reduce mortality effectively among patients with a high baseline VL. VL testing for all HIV patients is recommended at HIV diagnosis or on ART initiation.

Influence of weather variables on whitefly population build-up and progression of okra yellow vein mosaic virus disease

Influence of weather variables on whitefly population build-up and progression of okra yellow vein mosaic virus disease

Discovery of novel TMPRSS2 inhibitors for COVID-19 using in silico fragment-based drug design, molecular docking, molecular dynamics, and quantum mechanics studies

The global expansion of COVID-19 and the mutations of severe acute respiratory syndrome coronavirus necessitate quick development of treatment and vaccination. Because the androgen-responsive serine protease TMPRSS2 is involved in cleaving the SARS-CoV-2 spike protein allowing the virus to enter the cell, therefore, direct TMPRSS2 inhibition will inhibit virus activation and disease progression which make it an important target for drug discovery. In this study, a homology model of TMPRSS2 protein was initially developed. Then, we used the fragment-based drug design (FBDD) technique to develop effective TMPRSS2 inhibitors. Over a half-million fragments from the enamine database were screened for their binding ability to target protein, and then best-scoring fragments were linked to building new molecules with a good binding affinity. XP docking and MM-GBSA studies revealed 10 new formed molecules with docking score ≤ −14.982 kcal/mol compared to ambroxol (control) with a docking score of −6.464 kcal/mol. Finally, molecular dynamics (MD) and density functional theory (DFT) were calculated for the top 3 molecules.

Evaluation of MX1 Gene Promoter Methylation in Different Severities of COVID-19 Considering Patient Gender.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to a pandemic in March 2020. During a viral infection, it has been reported that epigenetic changes occur for both sides: Infected cells elicit an antiviral environmental response, which induces and initiates certain pathways for proper response to the virus, while the virus silences the expression of vital genes in the anti-viral host cell. In this study, we aimed to examine the methylation level of the MX1 gene promoter in different stages in COVID-19 patients compared to the control group. In total, 470 COVID-19 patients with a positive polymerase chain reaction (PCR) test (235 women and 235 men) were recruited into the study as the test group. Patients were divided based on the World Health Organization (WHO) classification into three groups: moderate, severe, and critical. Moreover, 100 healthy individuals (50 women and 50 men) were selected as the control group. Peripheral white blood cells were collected and PCR was performed using two types of primers designed for methylated and unmethylated states of the MX1 gene. The PCR products were then loaded on agarose gel and the band intensities were calculated by ImageJ software. The results showed a decrease in the methylation of the MX1 gene promoter in moderate and severe groups and an increase in the MX1 gene promoter methylation in the critical group. In addition, the level of methylation was higher in men than in women. Increased methylation of the MX1 gene in the critical group may indicate the role of SARS-CoV-2 in reducing the expression levels of this antiviral gene and thus promoting virus replication and disease progression.

Circulating level of sPD-1 and PD-1 genetic variants are associated with hepatitis B infection and related liver disease progression

Programmed cell death-1 (PD-1) variants and circulating level of soluble PD-1 are associated with susceptibility to malignant and infectious disease. This study aimed to examine the association of PD-1.5 and PD-1.9 variants, and plasma sPD-1 level with hepatitis B virus (HBV) infection and disease progression. The study cohort consisted of adults infected with HBV (n=513) - stratified by clinical course, including chronic hepatitis B (CHB, n=173), liver cirrhosis (LC, n=134) and hepatocellular carcinoma (HCC, n=206) - and matched healthy controls (HC, n=196). The PD-1.5 (rs2227981 C/T) and PD-1.9 (rs2227982 C/T) genetic variants were genotyped by Sanger sequencing, and plasma sPD-1 levels were quantified by enzyme immunoassay. Plasma sPD-1 levels were significantly higher among patients infected with HBV. The highest plasma sPD-1 levels were observed in patients with CHB, followed by patients with LC and HCC. In addition, the plasma sPD-1 levels correlated positively with liver inflammation [aspartate transaminase (AST): rho=0.57, P<0.0001; alanine aminotransferase: rho=0.57, P<0.0001], and were positively correlated with liver fibrosis [AST to platelet ratio index score: rho=0.53, P<0.0001). The PD-1.9 TT genotype was less common in patients with CHB compared with patients with LC, HCC, and HCC+LC in both codominant and recessive models (P<0.01), and was found to be a risk factor for HCC predisposition {HCC vs non-HCC: odds ratio (OR) 2.0 [95% confidence interval (CI) 1.13-3.7], Padj=0.017}. The PD-1.5 CT genotype was associated with reduced risk of acquiring HCC [OR 0.6 (95% CI 0.4-0.9), Padj=0.031]. sPD-1 level was associated with liver inflammation and progression of liver fibrosis, and the PD-1.5 and PD-1.9 variants were associated with HBV infection and progression of liver disease.

Drugs of Abuse and Their Impact on Viral Pathogenesis.

Commonly misused substances such as alcohol, cocaine, heroin, methamphetamine, and opioids suppress immune responses and may impact viral pathogenesis. In recent years, illicit use of opioids has fueled outbreaks of several viral pathogens, including the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). This review focuses on the myriad of mechanisms by which drugs of abuse impact viral replication and disease progression. Virus–drug interactions can accelerate viral disease progression and lead to increased risk of virus transmission.

Mold, Mycotoxins and a Dysregulated Immune System: A Combination of Concern?

Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding the role of mold and mycotoxins in the development of immune diseases. While the induction of allergic immune responses by molds is generally acknowledged, other direct health effects like the toxic mold syndrome are controversially discussed. However, recent observations indicate a particular importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system, due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and even human immunodeficiency virus (HIV) disease progression. In this review, we focus on the impact of mycotoxins regarding their impact on disease progression in pre-existing immune dysregulation. This is complemented by experimental in vivo and in vitro findings to present cellular and molecular modes of action. Furthermore, we discuss hypothetical mechanisms of action, where evidence is missing since much remains to be discovered.

Genetically edited hepatic cells expressing the NTCP-S267F variant are resistant to hepatitis B virus infection

The sodium-dependent taurocholate co-transporting polypeptide (NTCP)-S267F variant is known to be associated with a reduced risk of hepatitis B virus (HBV) infection and disease progression. The NTCP-S267F variant displays diminished function in mediating HBV entry, but its function in HBV infection has not been fully established in more biologically relevant models. We introduced the NTCP-S267F variant and tested infectivity by HBV in genetically edited hepatic cells. HepG2-NTCP clones with both homozygous and heterozygous variants were identified after CRISPR base editing. NTCP-S267F homozygous clones did not support HBV infection. The heterozygote clones behaved similarly to wild-type clones. We generated genetically edited human stem cells with the NTCP-S267F variant, which differentiated equally well as wild-type into hepatocyte-like cells (HLCs) expressing high levels of hepatocyte differentiation markers. We confirmed that HLCs with homozygous variant did not support HBV infection, and heterozygous variant clones were infected with HBV equally as well as the wild-type cells. In conclusion, we successfully introduced the S267F variant by CRISPR base editing into the NTCP/SLC10A gene of hepatocytes, and showed that the variant is a loss-of-function mutation. This technology of studying genetic variants and their pathogenesis in a natural context is potentially valuable for therapeutic intervention against HBV.

Vitamin D nemesis of COVID-19

The surge in the spread of the corona virus disease (COVID-19) pandemic alerted us to opt for the preventive medicine, as prevention is always better than cure. Apart from wearing mask, frequent hand washing and social distancing, strengthening our immune response plays a pivotal role in preventing infections. Vitamin D not only aids in calcium and phosphate homeostasis but also acts as an immunomodulator; the deficiency of which is linked with various respiratory and systemic infections. Hence we took up this review to study the effect of vitamin D in corona illness. Vitamin D exerts the expression of pro-inflammatory cytokines, hinders zinc metabolism, lowers Interleukin 6 levels and thereby inhibits cytokine storm in covid patients. Studies have proved that the covid patients have vitamin D deficiency and its supplementation improves the disease severity as well as the length of hospital stay. To conclude, Vitamin D supplementation can protect as well as halt the progression of corona virus disease. Further trials are needed to set the therapeutic levels in various stages of corona illness.

Revisiting Prognosis After Liver Transplant in Patients Positive for Hepatitis C Virus: Focus on Hepatitis C Recurrence-Unrelated Complications.

In this study, we revisited the reasons for poorer prognosis afterlivertransplantin patients with hepatitis C virus, whose main causes of death were generally known to be recurrent disease. Between April 2003 and March 2017, among 132 patients who underwent liver transplantbecause ofliver cirrhosis at ourinstitution, 40 patients (30.3%) were positive for hepatis C virus. We retrospectively compared the overall survival afterliver transplantin patients with and without hepatitis C virus infection. Furthermore, we investigated the causes of death in transplant recipients with hepatitis C virus infections. In patients with hepatitis C virus infection, overall survivalwas 82.2%, 75.2%, and50.8% at 1, 5, and 10 years,respectively, afterlivertransplant;these results were lower than those in patients without infection (94.5%, 87.0%, and 87.0% at 1, 5, and 10 years, respectively; P = .001). Among 40 patients with positive infection, 14 patients died after liver transplant. A main reason for death was hepatocellular carcinoma recurrence (3 patients). Surprisingly, only 1 patient died from hepatitis C virus-related complication (fibrosing cholestatic hepatitis); the remaining 10 patients died from reasons other than hepatitis C virus disease progression. Our results suggest that clinicians should not only be aware of hepatitis C virus recurrence but should also be aware of other unrelated complications in transplant recipients who are positive for this virus.

Association of interleukin-18 genotypes (-607C > A) and (-137 G > C) with the hepatitis B virus disease progression to hepatocellular carcinoma.

Chronic infection with HBV has been reported to be associated with the development of HCC. The inflammation mounted by cytokine-mediated immune system plays an important role in the pathogenesis of HBV-associated HCC. IL-18 is a pro-inflammatory cytokine whose role in the development of HBV-associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18, and expression level of its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR-RFLP. Genotypic distributions between the groups were compared using odd's ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression levels of pSTAT-1 and pNFƙB was determined by western blotting. In case of IL-18(- 607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(- 137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were significantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT-1 and pNF-κB) of IL-18 in stimulated PBMCs were significantly increased during HBV to HCC disease progression. These findings suggest that IL-18 has the potential to act as a biomarker of HBV-related disease progression to HCC.

HLA-associated preadaptation in HIV Vif is associated with higher set point viral load and faster CD4+ decline in Zambian transmission pairs.

We investigated the relationship between human leukocyte antigen (HLA)-associated preadaptation for the entire subtype C HIV-1 proteome of the transmitted founder virus and subsequent HIV-1 disease progression in a cohort of heterosexual linked transmission pairs in Zambia. An adaptation model was used to calculate an adaptation score for each virus-HLA combination in order to quantify the degree of preadaptation of the transmitted virus to the linked recipient's HLA alleles. These scores were then assessed for their relationship to viral load and longitudinal CD4+ decline in the recipient. Viral RNA was extracted from the plasma of the donor partner and the linked recipient near the time of transmission, as well as longitudinally from the linked recipient. Viral adaptation scores were calculated for each individual and each protein in the subtype C HIV-1 proteome. The majority of HLA-associated sites were located in Gag, Pol and Nef; however, proportional to protein length, the accessory and regulatory proteins contained a relatively high proportion of HLA-associated sites. Over the course of infection, HLA-mediated immune adaptation increased for all proteins except Vpu and gp120. Preadaptation was positively associated with higher early set point viral load and faster CD4+ decline. When examined by protein, preadaptation in Pol and Vif were statistically significantly associated with these markers of disease progression. Adaptation in Pol had the greatest impact on viral control. Despite containing a large proportion of HLA-associated sites, Vif was the only regulatory or accessory protein for which preadaptation significantly correlated with disease progression.

Expression profiling of miRNA-196a biomarker in naïve hepatitis C virus-infected and Sofosbuvir plus Daclatasvir-treated patients.

Micro-RNA (miRNA) is a short stretch of nucleotides that can regulate many genes associated with the various stages of the hepatitis C virus (HCV) life cycle and disease progression. This study evaluates the expression profiling of miRNA-196a in naïve HCV-infected, and Sofosbuvir plus Daclatasvir-treated patients. MiRNA-196a can inhibit HCV replication by silencing the HCV NS5A protein or downregulating the human BACH-I mRNA. The expression level of miRNA-196a was determined by quantitative reverse transcription PCR (RT-qPCR) using the whole RNA extracted from the recruited participant's serum. Results showed a 0.83-fold decrease in the miRNA-196a level in naïve HCV-infected than controls. On the contrary, an increase in the expression level by 0.06-fold was observed in Sofosbuvir plus Daclatasvir-treated patients. A negative but significant correlation was recorded between the HCV-RNA load and miRNA-196a expression level in the naïve-infected patients. Serum miRNA-196a ROC curve analysis revealed an area under the curve of 0.8278 (95% CI 0.7033-0.9524, p < 0.0001) with 82.05% sensitivity and 76.19% specificity in discriminating the healthy controls from the HCV-infected samples. In conclusion, our study explored the comparative expression levels of miRNA-196a in HCV-infected and Sofosbuvir plus Daclatasvir patients. Further studies are needed to examine the possible role of miR-196a as a therapeutic agent for treating HCV-infected patients.