• Clinical and Experimental Pediatrics
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• v.62 no.3
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• pp.108-112
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• 2019

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha ($IFN-{\alpha}$) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of $IFN-{\alpha}$ therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular $IFN-{\alpha}$ therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular $IFN-{\alpha}$ treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular $IFN-{\alpha}$ treatment in patients with SSPE.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.109-115
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• 2001

Background: The role of the interferon consensus sequence binding protein (ICSBP), a member of interferon regulatory factor family, in protecting against a vesicular stomatitis virus (VSV) infection has not been firmly elucidated. Thus, it was investigated utilizing the human promyelocytic leukemia HL-60 cells which do not express ICSBP. Methods: HL-60 cells were stably transfected with plasmid containing cDNA for either ICSBP or DNA binding domain (DBD) and tested for their VSV-susceptibilities. The susceptibility of each transfectant group to a VSV infection was determined by a plaque assay at 1 h, 24 h, and 48 h post-infection in the presence (500 IU/ml) or absence of interferon ${\alpha}$ ($IFN{\alpha}$). Results: In the absence of $IFN{\alpha}$, the three groups showed similar sensitivities to a VSV infection. However, when pre-treated with IFN, the viral titers in both the ICSBP and control clones steadily decreased over 48 h of incubation, indicating the existence of $IFN{\alpha}$-mediated protection against VSV infection. The $IFN{\alpha}$-treated ICSBP clones appeared to be more resistant to infection compared with the control clones, although the difference was not great. On the contrary, the viral titers in the $IFN{\alpha}$-treated DBD clones increased at 24 h then decreased by 48 h. Conclusion: The expression of truncated ICSBP (DBD) does not appear to underlie the impaired protection against a VSV infection in the DBD clones, since even the control clones lacking ICSBP were protected from a VSV infection. This suggests that ICSBP does not play a critical role in the $IFN{\alpha}$- mediated anti-VSV response of HL-60 cells, although it appears to confer some resistance to a VSV infection.

• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.427-438
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• 2020

Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

• The Journal of the Korean dental association
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• v.47 no.8
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• pp.522-533
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• 2009

Purpose: Infection with HIV-1 virus has become a critical worldwide public health problem. The oral complications of HIV infection with its progression of impairment of the host response to combat infection present unique challenges to the periodontists. Material and Methods : Medline research was carried out to find relationship of the progression of HIV infection to the occurrence of oral lesions including the HIV-related periodontal diseases. Results: The linear gingival erythema, necrotizing ulcerative periodontitis, necrotizing ulcerative gingivitis and oral candidiasis are common lesions in HIV-infected individuals. The linear gingival erythema and necrotizing ulcerative periodontitis lesions in HIV-infected subjects were found to have a similar microbiological profile. There are several general considerations in the periodontal management of the HIV-infected patient with or without periodontal disease. The altered immunity and host response in patients with HIV infection may also affect the incidence and severity of other common forms of periodontal disease not associated with HIV infection. Conclusion: Periodontal diseases in HIV-infected individuals present unique challenges in diagnosis, monitoring, treatment and maintenance. Therefore exact HIV staging, geographic location, antiviral and antimicrobial therapies and oral habits should be taken into consideration when treating HIV-infected patients.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.225-231
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• 2014

In this study we aim to extensively investigate the anti-influenza virus immune responses in human pharyngeal epithelial cell line (Hep-2) and evaluate the protective role of Toll-like receptor (TLR) ligands in seasonal influenza A H1N1 (sH1N1) infections in vitro. We first investigated the expression of the TLRs and cytokines genes in resting and sH1N1 infected Hep-2 cells. Clear expressions of TLR3, TLR9, interleukin (IL)-6, tumour necrosis factor (TNF)-${\alpha}$ and interferon (IFN)-${\beta}$ were detected in resting Hep-2 cells. After sH1N1 infection, a ten-fold of TLR3 and TLR9 were elicited. Concomitant with the TLRs activation, transcriptional expression of IL-6, TNF-${\alpha}$ and IFN-${\beta}$ were significantly induced in sH1N1-infected cells. Pre-treatment of cells with poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) resulted in a strong reduction of viral and cytokines mRNA expression. The results presented indicated the innate immune response activation in Hep-2 cells and affirm the antiviral role of Poly I:C and CpG-ODN in the protection against seasonal influenza A viruses.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.113-121
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• 2011

Foot-and-mouth disease (FMD) is a severe vesicular disease of cloven-hoofed animals including domesticated ruminants and pigs. Acute clinical signs may be mild in sheep and goats but are associated with lameness in pigs and mouth lesions with vesicles in cattle. The required condition for a successful pathogen appears to be the ability to counteract both the host innate and adaptive immune response. FMD virus (FMDV) inhibits the induction of antiviral molecules and interferes with the secretory pathway in the infected cell. The surface expression of Major Histocompatibility Complex (MHC) class I molecules is reduced in infected cells. Thus, the ability of the host to recognize and eliminate virus infected cells is decreased. Furthermore, FMDV infection results in a rapid, but transient lymphopenia, reducing the number of T and B cells, and affecting T cell function. The virus appears to premature apoptosis-mediated cell death because it has a very short replication cycle and is able to rapidly produce large amounts of virus. FMDV engages the host protective response at multiple steps to ensure its effective replication and pathogenesis. This review describes the recent pathological and immunological studies to overcome the powerful abilities of FMDV to counteract defense mechanism of host.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.150-160
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• 2017

Background: Recently, a fixed combination of grazoprevir and elbasvir (GE) has been introduced to the arsenal of chemotherapeutics to fight against this virus. The study aimed to provide information on the efficacy and safety of GE for the treatment of HCV infection by performing a meta-analysis of literature data. Methods: PubMed and EMBASE database searches were conducted. Among the literature retrieved, pivotal Phase III clinical studies were analyzed. Statistical analysis of the data was performed by RevMan. Results: Four pivotal Phase III clinical studies compared the efficacy and safety of GE. When HCV patients were treated with GE for 12 weeks, the sustained virologic response, defined as the viral RNA level below the lower limit of quantification at 12 weeks after the cessation of therapy (SVR12), was 94.7%. The clinical advantage of GE involves its use by patients with cirrhosis and/or renal failure without dose adjustment. If the genotype (GT) of the causative virus was GT1a with NS5A polymorphism or GT4 with resistance to peginterferon/ribavirin, treatment with GE plus ribavirin for 16 weeks resulted in a better outcome compared to treatment with GE alone for 12 weeks. Adverse events reported during the four clinical studies were 71.09% in the GE arms and it was 76.61% in the non-GE arms, with the most frequent events being mild central nervous system symptoms. Conclusion: GE was generally safe and effective for the treatment of HCV infection. However, since HCV mutates very rapidly and becomes resistant to antiviral agents, long-term monitoring should be mandatory.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1037-1040
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• 2015

Hepatitis C is a blood-borne infectious disease of liver, caused by a small enveloped, positive-single stranded RNA virus, called the hepatitis C virus (HCV). HCV belongs to the Flaviviridae family and has 6 genotypes and more than 100 subtypes. It is estimated that 185 million people are infected with HCV worldwide and 5% of these are in Pakistan. The study was designed to evaluate different genotypes of HCV circulating in District Mardan and to know about the behavior of these genotypes to different anti-viral regimes. In this study 3,800 patients were exposed to interferon alfa-2a plus Ribavirin treatment for 6-months and subjected to real-time PCR to check the viral response. Among these 3,677 (97%) patients showed no detectable HCV RNA while 123 (3%) patients (non-responders) remained positive for HCV RNA. Genotypes of their analyzed showed that most of them belonged to the 3a genotype. Non-responders (123) and relapsed (5) patients were subjected to PEG-interferon and Ribavirin therapy for next 6 months, which resulted into elimination of HCV RNA from 110 patients. The genotypes of the persisting resistant samples to anti-viral treatment were 3b, 2a, 1a and 1b. Furthermore, viral RNA from 6 patients remained un-typed while 4 patients showed mixed infections. HCV was found more resistant to antiviral therapy in females as compared to mals. The age group 36-45 in both females and males was found most affected by infection. In general 3a is the most prevalent genotype circulating in district Mardan and the best anti-viral therapy is PEG-interferon plus Ribavirin but it is common practice that due to the high cost patients receive interferon alfa-2a plus Ribavirin with consequent resistance in 3% patients given this treatment regime.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8665-8670
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• 2016

Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2485-2490
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• 2016

The liver is one of the most common sites of cancer in the world, hepatocellular carcinoma (HCC) predominating. HCC is the sixth most common cancer and the third leading cause of cancer related death overall. Hepatitis C is a major risk factor and HCV is a rapid spreading virus which has become a problem globally, including in Pakistan. Interferon alpha therapy is used against HCV disease to regulate cell reproduction and to boost the immune system. In minute amounts interferon alpha is produced naturally by the immune system in HCV patients in response to hepatitis C virus and binds to receptors in the target cells and starts transcription of 20-30 genes due to which it develops an antiviral influence. Interferon is also administered artificially to overcome HCV disease and remove the biological effect of the virus from the infected site. The use of interferon or Peg-IFN plus Ribavirin treatment is also associated with adverse effects on body. For the current study, a convenient sample of 156 HCV positive patients of both males and females were taken. To collect blood CP and ALT, a reduction of level data and other important information were collected from the patients at regular intervals. Findings were 11.4 % in the red blood cells (RBC), 9.64 % in the total leukocyte count (WBC), 8.4 % in the hemoglobin levels (HB), 30.3 % in the platelet (Plt) count in both sexes. There was significant reduction in ALT levels due to Pegylated interferon plus ribavirin therapy. Hence strict haemotological monitoring of blood CP and ALT levels is necessary at regular intervals to reduce severe side effects which may lead to morbidity and mortality.