In silico and in vitro assay of Hexagamavunon-6 analogs, Dibenzilyden-N-Methyl-4-piperidone as antibacterial agents

A new series of analogs Hexagamavunon-6 (HGV-6) was prepared and screened for antibacterial activity againstStreptococcus mutans (ATCC 25175), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Psedomonasaeruginosa (ATCC 27853), Klebsiella pneumoniae, and Enterococcus faecalis (ATCC 29212) using disk diffusionmethod. The antibacterial results showed that 3,5-Bis-(2',4'-dichlorobenzilyden)-N-methyl-4-piperidone (1c)compound display significant inhibition and broad-spectrum antibacterial activity. This is in accordance with the insilico evaluation showing that compound 1c has a lower docking score than both compounds 1a and 1b. None of thetested compounds were as active as the reference standard drug Amoxicillin.

Seroprevalence of Hepatitis G Virus IgG Antibody among Blood Donors, Pregnant Women, Neonates and Apparently Healthy Population.

This cross sectional and observational study was conducted in the Department of Microbiology, Sylhet MAG Osmani Medical College, Sylhet, during the period from 1st January 2012 to 31st December 2012 with a view to explore the seropositivity of Hepatitis G virus (HGV) in blood donors, pregnant women, new born and apparently healthy subjects. For this purpose 45 blood donors, 45 pregnant women, 45 new born babies of same mothers and 45 apparently healthy subjects were selected according to the inclusion and exclusion criteria. The HGV antibody was measured in venous blood from blood donor, pregnant women and apparently healthy subjects; and cord blood from newborn babies with a commercially available enzyme-linked immunosorbent assay (ELISA) method. The mean age of the blood donors, pregnant women and healthy subjects was 24.9 (SD ± 3.5) years; 24.9 (SD ± 3.5) years and 22.1 (SD ± 1.5) years respectively. The overall seropositivity of HGV was 3 (1.7%). The seropostivity of HGV of blood donors, new born babies and healthy subjects was 1 (2.2%) in each group but no HGV antibody positivity among the pregnant women (p=0.797). Among the male patients 2 (2.2%) patients were seropositive for HGV; while in female patients, 1 (1.1%) patient was seropositive for HGV (p=0.547). Among the patients with previous blood transfusion 1 (1.9%) patient was seropositive for HGV; while among patients without previous blood transfusion 2 (1.6%) patients were seropositive for HGV (p=0.882). This study yielded that there is high prevalence of HGV seropositivity among population in this region of Bangladesh. So, screening of blood units for HGV would deserve consideration.

Interacción entre el virus de la inmunodeficiencia humana y el virus GB tipo-C durante el estado de co-infección / Interaction between HIV-1 and GB virus type-C during coinfection status

The human immunodeficiency virus (HIV) infection is one of the most important problems in public health. It is estimated that 3 3 million people are infected around the world. HIV and GBV-C share the same transmission route, being frequent the co-infection. Since both viruses replicate in CD4+ lymphocytes, recent studies have described an interaction. Decreasing of HIV viral load and higher CD4 counts have been observed in co-infected patients, leading a better clinical outcome. Nevertheless, some epidemiological studies have shown contradictory results. Additionally, in vitro models report inhibition of HIV by E1, E2, NS3 and NS5A GBV-C proteins, resulting in a decreasing of p24 antigen. This review summarizes the principal findings about co-infection and mechanisms that have been proposed for HIV-1 inhibition.

La infección por el virus de la inmunodeficiencia humana (VIH) continúa siendo uno de los principales problemas en salud pública; se estima que existen actualmente más de 33 millones de personas infectadas en el mundo. El VIH y el virus GB tipo C (GBV-C) comparten la misma vía de transmisión, por lo que es frecuente encontrar individuos co-infectados. Estudios recientes han descrito un efecto inhibitorio asociado a disminución en la carga viral de VIH, altos recuentos de CD4 y mayor tiempo de sobrevida en pacientes co-infectados, resultando en un mejor pronóstico y menor progreso a SIDA; adicionalmente, estudios in vitro indican que las proteínas virales E1, E2, NS3 y NS5A del GBV-C estarían implicadas en la inhibición del VIH-1. En el presente artículo se revisan los principales aspectos de la co-infección, y se describen los mecanismos propuestos para la inhibición de la replicación del VIH-1 mediada por las proteínas virales del GBV-C.

Influence of GB virus C on IFN-γ and IL-2 production and CD38 expression in T lymphocytes from chronically HIV-infected and HIV-HCV-co-infected patients

This study was designed to assess the effect of GB virus (GBV)-C on the immune response to human immunodeficiency virus (HIV) in chronically HIV-infected and HIV- hepatitis C virus (HCV)-co-infected patients undergoing antiretroviral therapy. A cohort of 159 HIV-seropositive patients, of whom 52 were HCV-co-infected, was included. Epidemiological data were collected and virological and immunological markers, including the production of interferon gamma (IFN-γ) and interleukin (IL)-2 by CD4, CD8 and Tγδ cells and the expression of the activation marker, CD38, were assessed. A total of 65 patients (40.8 percent) presented markers of GBV-C infection. The presence of GBV-C did not influence HIV and HCV replication or TCD4 and TCD8 cell counts. Immune responses, defined by IFN-γ and IL-2 production and CD38 expression did not differ among the groups. Our results suggest that neither GBV-C viremia nor the presence of E2 antibodies influence HIV and HCV viral replication or CD4 T cell counts in chronically infected patients. Furthermore, GBV-C did not influence cytokine production or CD38-driven immune activation among these patients. Although our results do not exclude a protective effect of GBV-C in early HIV disease, they demonstrate that this effect may not be present in chronically infected patients, who represent the majority of patients in outpatient clinics.

Detection of GBV-C/HGV RNA in cervico-vaginal smears from healthy individuals

The purpose of the present study was to evaluate the sexual transmission of GBV-C/HGV, through RNA detection in cervicovaginal smears. Therefore the GBV-C/HGV RNA in cervicovaginal smears from apparently healthy women was investigated using routine proceedings for prophylactic screening to cervical cancer. GBV-C/HGV RNA was detected by reverse transcriptase and polymerase chain reaction (RT-PCR). Only one woman presented co-infection with human papilloma virus (HPV). The GBV-C/HGV RNA was detected in 13/73 (17.57 percent) healthy women and it's prevalence in participating women between 28-43 years old was 53.85 percent. No association was found with GBV-C/HGV for the age of first sexual intercourse and number of pregnancies. In GBV-C/HGV RNA positive women, 69.23 percent were married. In conclusion, the present findings show that cervical and vaginal specimens could contain the GBV-C/HGV RNA.

O objetivo do presente estudo foi avaliar a transmissão sexual de GBV-C/HBV, através da detecção do RNA viral em raspados cérvico-vaginais. Portanto, a presença do RNA GBV-C/HGV foi investigada em raspados cérvico-vaginais em mulheres aparentemente saudáveis que realizaram exames preventivos para câncer cervical. GBV-C/HGV RNA foi detectado por reação de transcriptase reversa e reação em cadeia da polimerase (RT-PCR). Apenas uma mulher apresentou a co-infecção com o papiloma vírus humano (HPV). O RNA GBV-C/HGV foi detectado em 13/73 (17,57 por cento) mulheres saudáveis e sua prevalência entre participantes da idade de 28-43 anos foi de 53,85 por cento. Não foi observada relação entre a presença do RNA GBV-C/HGV com a idade de primeira relação sexual, nem com o número de gestações. Entre as mulheres que apresentavam o RNA viral, 69,23 por cento eram casadas. O presente estudo demonstrou que secreções cérvico-vaginais podem conter o RNA viral GBV-C/HBV.

Detection of HGV-RNA in the blood donors and patient with HBV or HCV by RT-PCR / 吉林大学学报(医学版)

Objective:To discuss the clinical significance of overlapping infection of HGV in blood donorsand viral hepatitis. Methods :HGV-RNA was detected by reverse transcription-polymerase chain reaction.Results :The infectious rate of HGV in blood donors was 4% ,that in the patients with HBV and HCV was13. 9% and 15.8% respectively. Conclusion:Our results indicate that the HGV infection was widespread.Further study of immune response and status of viral replication in the liver tissue in overlapping infectionwith HBV and HCV,was needed.

Prevalence of Hepatitis G Virus Infection in Patients with Chronic Renal Failure / 대한간학회지

BACKGROUNDS/AIMS: To investigate the prevalence and clinical implications of hepatitis G virus (HGV) infection in patients with chronic renal failure, a cross-sectional study of 131 hemodialysis patients and 33 kidney transplantation recipients was conducted. METHODS: HGV RNA was amplified by reverse-transcription (RT) polymerase chain reaction (PCR) assay with primers from the 5'-untranslated region of the viral genome. RESULTS: The prevalence of HGV infection in patients with chronic renal failure was 25%(41/164). The following factors were taken into consideration: the mean age(43.15+/-11.97 years vs 46.46+/-13.08 years), the male to female ratio(2.15:1 vs 1.86:1), the mean of the dialysis duration(4.58+/-3.18 years vs 3.90+/-3.31 years), transfusion history (75.6% vs 62.6%), the mean of the ALT level during the prior 6 months(25.78+/-21.50 IU/L vs 23.00+/-59.49 IU/L), and the amount of transfusion(6.22+/-8.03 units vs 5.74+/-9.44 units). The anti-HCV(4.88% vs 8.94%) showed no difference between HGV RNA positive and negative group. The HBsAg positive ratio was 19.5% and 5.81% in HGV RNA positive group and negative group, respectively. CONCLUSION: The prevalence of HGV infection in patients with chronic renal failure was 25%. There was a higher rate of HBsAg positivity in the HGV RNA positive group rather than in the negative group. HGV infection did not seem to be associated with clinically significant hepatitis.

Molecular characterization of hepatitis G virus (HGV) isolates from healthy adults and risk groups in the Philippines

Hepatitis G virus (HGV) infection has been detected in Filipinos through a prospective study of 1,088 blood samples. HGV RNA was found in sera of 6/516 (1.2 percent) healthy adults (volunteer blood donors), 11/138 (8.0 percent) chronic liver disease patients, 7/207 (3.4 percent) hemodialysis patients, and 14/227 (6.2 percent) multiply transfused patients using reversetranscription polymerase chain reaction (RT-PCR) with random hexamer primers and a set of PCR primers from the 5 untranslated region (5UTR) of the HGV genome. A total of 38/1,088 subjects were HGV RNA-positiveThe PCR products derived from the 5UTR of HGV RNA+ samples were sequenced to determine the genotypic variant of HGV in the Philippines. Pairwise alignment of sequences and phylogenetic tree construction revealed that among the five known HGV genotypic variants, the Philippine isolates are most closely related to the Asian type (III)Considering that HGV is a highly mutable organism, surveillance for new genotypes may be the only way to assess accurate asymptomatic infection rates. How much this virus evolves in the future may have an impact on its virulence, transmissibility and invasiveness. It is therefore important, from an evolutionary perspective, to continue and monitor evolution of HGV specifically with studies at the molecular level. (Author)

Original Articles: The Detection of Hepatitis G Virus RNA by RT - PCR in Various Liver Diseases / 대한간학회지

BACKGROUND/AIMS: Recently, nucleotide sequences from a novel virus, termed hepatitis G virus (HGV), were identified in serum from a patient with cryptogenic hepatitis and suggested as agent of non A-E hepatitis. HGV has been isolated from patients with various liver diseases but clinical implications of this new agent remain largely unresolved. In Korea, the etiology of substantial fraction of hepatitis has remained undefined and there has been no report concerning HGV. METHODS: To determine the infection rate of HGV, RT-PCR of 5 UTR of HGV was performed, and to understand the clinical implication of HGV, medical records of 115 patients with various liver diseases were reviewed. Of 115 patients, 63 were male and 52 were female. Their mean age was 44 years (19-74) and their mean AST and ALT were 121.3+278.7 IU/L and 172.2+253.3 IU/L, respectively. Of 115 patients, 58 (50.4%) had no specific cause of liver diseases, 37 (32.2%) were infected with hepatitis B and/or C virus and 20 (17.4%) had non-viral identifiable liver diseases. RESULTS: 1. HGV RNA was detected in 15 (13.0%) patients of 115 patients. 2, Among the 15 HGV RNA positive cases, 7 were male and 8 were female. Their mean age was 48 years (19-72) and their mean AST and ALT were 71.9+45.2 IU/L, 97.4+66.8 IU/I respectively. 3. HGV RNA was detected in 8(13.8%) of 58 patients without obvious causes of their liver diseases and in 7 (18.9%) of 37 patients infected with HBV and/or HCV. However, HGV RNA was not detected fram 20 patients with non-viral liver diseases such as alcoholic liver diseases, autoimmune hepatitis, PBC, or fatty liver. 4. HGV RNA was detected in 5 (19.2%) of 26 patients with acute hep- atitis, in 6 (9.4%) of 64 patients with chronic hepatitis, in 1 (14.3%) of 7 patients with liver cirrhasis, and iB 3 (27.3%) Of 11 pafients with hepatocellular caIcinoma. 5. These was no slatistically significant difference in sex, age, history of transfusion, serum ALT level, etiologies and status of liver diseases between HGV RNA positve and negative group. CONCLUSIONS: the prevalence of HGV infection is quite high among the patients who have no specific cause of acute or chronic liver diseases and HGV can be coinfected with HBV and/ar HCV infection in Korea.

STUDIES OF HEPG2 CELLS INFECTED WITH HGV RNA GENOME / 微生物学通报

In order to observe the replication and expression of HGV RNA genome in HepG2 cells and establish a cell model of HGV infection, HGV RNA genome was prepared in vitro and transfected HepG2 cells with lipofec-tamin. HGV RNA-positive supernatants were used to infect fresh HepG2 cells. RT-PCR, immunohistochemistry and Western blot assays were carried out to detect the replication and expression of HGV in HepG2 cells. Both positive and negative strands of HGV RNA could be detectable in cell culture supernatants and cells at 24h post-transfection. During the culture periods of 90 days, the cells were maintained by changing the medium every 3 or 5 days, and cultured for more than 20 passages. Both strands of HGV could be detectable in culture supernatants and cells. Immunohistochemistry and Western blot results also confirmed that HGV E2 protein could be expressed in the infected HepG2 cells. HGV RNA could also be detectable in the frozen-thawed HepG2 cells infected with HGV RNA genome. Therefore, HGV RNA genome can replicate and express in HepG2 cells, this HGV RNA genome transfected cells model could be used as a cell model in the studies of replication and infection of HGV.