scholarly journals Modified comb-shaped antisense oligonucleotides may secure us against many important viral diseases including AIDS

2021 ◽  
Author(s):  
Ahmed Ibrahim
Keyword(s):  
Hepatitis C ◽  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
Viral Diseases ◽  
Genomic Rna ◽  
Cdna Synthesis ◽  
Hiv Replication ◽  
Strong Promoter ◽  
R Region ◽  
Hiv 1

Abstract To inhibit HIV replication and infection, we have designed novel linear single stranded modified antisense nucleic acid oligonucleotides ending with or without chain terminating bases (Which resemble the shape of the comb). They were targeting specifically the HIV-1 clone pNL4-3 strong promoter pre PBS region to stop cDNA synthesis within or before the R region, preventing the viral reverse transcriptase (RT) jumping to the 3' end and continue copying the virus. The main advantages of our comb shaped oligonucleotides are their specificity and extreme protection against resistance by known viral mutations. Promising results were obtained for two 15-mer compounds at one tenth azidothymidine concentration. As a result we claim that when adapted properly, the comb shaped antivirals can be used to target the genomic RNA of a number of serious viruses such as for example Ebola, SARS-CoV-2, Influenza, Dengue, hepatitis C, Chikungunya and Zika as they are all using polymerases to copy their genomic RNA1-8. Their genomic RNA could be destroyed through the human or viral endonucleases instead of the viral RT RNAseH site when their polymerases are stopped at specific sites.

scholarly journals Human Cellular Nucleic Acid-Binding Protein Zn2+ Fingers Support Replication of Human Immunodeficiency Virus Type 1 When They Are Substituted in the Nucleocapsid Protein

2003 ◽  
Vol 77 (15) ◽  
pp. 8524-8531 ◽  
Author(s):  
Connor F. McGrath ◽  
James S. Buckman ◽  
Tracy D. Gagliardi ◽  
William J. Bosche ◽  
Lori V. Coren ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Nucleic Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Structural Characteristics ◽  
Nucleic Acid Binding ◽  
Genomic Rna ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A family of cellular nucleic acid binding proteins (CNBPs) contains seven Zn2+ fingers that have many of the structural characteristics found in retroviral nucleocapsid (NC) Zn2+ fingers. The sequence of the NH2-terminal NC Zn2+ finger of the pNL4-3 clone of human immunodeficiency virus type 1 (HIV-1) was replaced individually with sequences from each of the seven fingers from human CNBP. Six of the mutants were normal with respect to protein composition and processing, full-length genomic RNA content, and infectivity. One of the mutants, containing the fifth CNBP Zn2+ finger (CNBP-5) packaged reduced levels of genomic RNA and was defective in infectivity. There appear to be defects in reverse transcription in the CNBP-5 infections. Models of Zn2+ fingers were constructed by using computational methods based on available structural data, and atom-atom interactions were determined by the hydropathic orthogonal dynamic analysis of the protein method. Defects in the CNBP-5 mutant could possibly be explained, in part, by restrictions of a set of required atom-atom interactions in the CNBP-5 Zn2+ finger compared to mutant and wild-type Zn2+ fingers in NC that support replication. The present study shows that six of seven of the Zn2+ fingers from the CNBP protein can be used as substitutes for the Zn2+ finger in the NH2-terminal position of HIV-1 NC. This has obvious implications in antiviral therapeutics and DNA vaccines employing NC Zn2+ finger mutants.

scholarly journals Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication

FEBS Letters ◽  
2004 ◽  
Vol 578 (3) ◽  
pp. 285-290 ◽  
Author(s):  
Joacim Elmén ◽  
Hong-Yan Zhang ◽  
Bartek Zuber ◽  
Karl Ljungberg ◽  
Britta Wahren ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Virus Replication ◽  
Antisense Oligonucleotides ◽  
Locked Nucleic Acid ◽  
Inhibit Virus Replication ◽  
Genome Dimerization ◽  
Hiv 1

scholarly journals Human immunodeficiency virus, hepatitis C and hepatitis B infections among blood donors in Germany 2000-2002: risk of virus transmission and the impact of nucleic acid amplification testing

2005 ◽  
Vol 10 (2) ◽  
pp. 13-14 ◽  
Author(s):  
Ruth Offergeld ◽  
D Faensen ◽  
S Ritter ◽  
O Hamouda
Keyword(s):  
Hepatitis C ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Blood Supply ◽  
Blood Donation ◽  
Mathematic Model ◽  
Nucleic Acid Amplification ◽  
Window Period ◽  
The Impact ◽  
Hiv 1

Blood and plasma donations in Germany are collected by several institutions, namely the German Red Cross, community and hospital-based blood services, private blood centres, commercial plasma donation sites and transfusion services of the army. All blood donation centres are required to report quarterly data on infection markers to the Robert Koch Institute, thus providing current and accurate epidemiological data. The prevalence and incidence of relevant viral infections are low in the blood donor population in Germany, with a decreasing trend for hepatitis C infections in new and repeat donors since 1997. The implementation of mandatory nucleic acid amplification technique (NAT) testing for hepatitis C virus (HCV) in 1999 has markedly improved transfusion safety. HIV-NAT became mandatory in 2004 but was done voluntarily by the majority of the blood donation services before then. The potential benefit of hepatitis B virus (HBV) minipool NAT is not as clear because chronic HBV carriers with very low virus levels might donate unidentified. The residual risk of an infectious window period donation inadvertently entering the blood supply can be estimated using a mathematic model which multiplies the incidence rate by the number of days during which an infection may be present but not detectable, i.e. the length of the window period. The risk of an undetected infection without NAT testing was estimated to be 1 in 2 770 000 for HIV, 1 in 670 000 for HCV and 1 in 230 000 for HBV in 2001/2002. This contrasts with 1 in 5 540 000 for HIV, 1 in 4 400 000 for HCV and 1 in 620 000 for HBV with minipool NAT testing. This demonstrates that NAT testing can further reduce the already very small risk of infectious donations entering the blood supply.

Ultrastructural observations of human monocytes infected with HIV-1

1991 ◽  
Vol 49 ◽  
pp. 108-109
Author(s):  
James K. Koehler ◽  
Steven G. Reed ◽  
Joao S. Silva
Keyword(s):  
Gradient Centrifugation ◽  
Virus Production ◽  
Human Monocyte ◽  
Red Cross ◽  
Human Monocytes ◽  
Blood Monocytes ◽  
Hiv Replication ◽  
Electron Microscopic ◽  
Ultrastructural Studies ◽  
Hiv 1

As part of a larger study involving the co-infection of human monocyte cultures with HIV and protozoan parasites, electron microscopic observations were made on the course of HIV replication and infection in these cells. Although several ultrastructural studies of the cytopathology associated with HIV infection have appeared, few studies have shown the details of virus production in “normal,” human monocytes/macrophages, one of the natural targets of the virus, and suspected of being a locus of quiescent virus during its long latent period. In this report, we detail some of the interactions of developing virons with the membranes and organelles of the monocyte host.Peripheral blood monocytes were prepared from buffy coats (Portland Red Cross) by Percoll gradient centrifugation, followed by adherence to cover slips. 90-95% pure monocytes were cultured in RPMI with 5% non-activated human AB serum for four days and infected with 100 TCID50/ml of HIV-1 for four hours, washed and incubated in fresh medium for 14 days.

The diagnosis of hepatitis C viral infection

2014 ◽  
Vol 155 (26) ◽  
pp. 1019-1023
Author(s):  
Judit Gervain
Keyword(s):  
Hepatitis C ◽  
Nucleic Acid ◽  
Viral Infection ◽  
Structural Changes ◽  
Viral Infections ◽  
Transient Elastography ◽  
Viral Nucleic Acid ◽  
Length Of Treatment ◽  
Subtype B

The successful therapy of hepatitis C viral infection requires that the illness is diagnosed before the development of structural changes of the liver. Testing is stepwise consisting of screening, diagnosis, and anti-viral therapy follow-up. For these steps there are different biochemical, serological, histological and molecular biological methods available. For screening, alanine aminotransferase and anti-HCV tests are used. The diagnosis of infection is confirmed using real-time polymerase chain reaction of the viral nucleic acid. Before initiation of the therapy liver biopsy is recommended to determine the level of structural changes in the liver. Alternatively, transient elastography or blood biomarkers may be also used for this purpose. Differential diagnosis should exclude the co-existence of other viral infections and chronic hepatitis due to other origin, with special attention to the presence of autoantibodies. The outcome of the antiviral therapy and the length of treatment are mainly determined by the viral genotype. In Hungary, most patients are infected with genotype 1, subtype b. The polymorphism type that occurs in the single nucleotide located next to the interleukin 28B region in chromosome 19 and the viral polymorphism type Q80K for infection with HCV 1a serve as predictive therapeutic markers. The follow-up of therapy is based on the quantitative determination of viral nucleic acid according to national and international protocols and should use the same method and laboratory throughout the treatment of an individual patient. Orv. Hetil., 2014, 155(26), 1019–1023.

The prevalence of hepatitis B and C co-infections among people with HIV-1 in Bulgaria: 2010–2015

2019 ◽  
Vol 14 (12) ◽  
pp. 791-798
Author(s):  
Ivailo Alexiev ◽  
Elitsa Golkocheva-Markova ◽  
Asya Kostadinova ◽  
Reneta Dimitrova ◽  
Lora Nikolova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hcv Rna ◽  
B Virus ◽  
Sex With Men ◽  
Multiple Risk Behavior ◽  
Hiv 1 ◽  
Hiv Aids

Aim: To evaluate hepatitis B virus (HBV) and hepatitis C virus (HCV) among individuals with HIV/AIDS in Bulgaria diagnosed between 2010 and 2015. Materials & methods: A total of 1158 individuals were diagnosed with HIV/AIDS during the study period. Different transmission groups were tested with ELISA and real-time PCR for HBV and HCV markers. Results: Hepatitis B surface antigen and hepatitis C virus antiboby were found in 9.3 and 23.2% of the tested. HBV DNA and HCV RNA has been found in 47.4 and 69.6%. Hepatitis B and C co-infections were predominant in multiple risk behavior groups, including people who inject drugs, men who have sex with men, prisoners and Roma individuals. Conclusion: HIV prevalence in Bulgaria is low but the rates of hepatitis B and C co-infections among these patients fall within the upper range reported in Europe.

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