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1.
Viruses ; 13(5)2021 04 28.
Article in English | MEDLINE | ID: mdl-33924859

ABSTRACT

Infection with influenza A and B viruses results in a mild to severe respiratory tract infection. It is widely accepted that many factors affect the severity of influenza disease, including viral replication, host adaptation, innate immune signalling, pre-existing immunity, and secondary infections. In this review, we will focus on the interplay between influenza virus RNA synthesis and the detection of influenza virus RNA by our innate immune system. Specifically, we will discuss the generation of various RNA species, host pathogen receptors, and host shut-off. In addition, we will also address outstanding questions that currently limit our knowledge of influenza virus replication and host adaption. Understanding the molecular mechanisms underlying these factors is essential for assessing the pandemic potential of future influenza virus outbreaks.


Subject(s)
Host-Pathogen Interactions/immunology , Immunity, Innate , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Orthomyxoviridae/genetics , Orthomyxoviridae/immunology , RNA, Viral/biosynthesis , Virus Replication , Animals , DNA-Directed RNA Polymerases , Humans , Influenza, Human/immunology , Influenza, Human/virology , Receptors, Virus/metabolism , Viral Proteins
2.
Nat Commun ; 11(1): 5432, 2020 10 28.
Article in English | MEDLINE | ID: mdl-33116134

ABSTRACT

Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and for countless gene transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline that enables the direct side-by-side comparison of pre-selected AAV capsids in high-throughput and in the same animal, by combining DNA/RNA barcoding with multiplexed next-generation sequencing. For validation, we create three independent libraries comprising 183 different AAV variants including widely used benchmarks and screened them in all major tissues in adult mice. Thereby, we discover a peptide-displaying AAV9 mutant called AAVMYO that exhibits superior efficiency and specificity in the musculature including skeletal muscle, heart and diaphragm following peripheral delivery, and that holds great potential for muscle gene therapy. Our comprehensive methodology is compatible with any capsids, targets and species, and will thus facilitate and accelerate the stratification of optimal AAV vectors for human gene therapy.


Subject(s)
Capsid Proteins/genetics , Dependovirus/genetics , Genetic Vectors , Muscles/metabolism , Muscles/virology , Animals , Capsid , DNA Barcoding, Taxonomic , Female , Gene Library , Genetic Therapy/methods , Genetic Variation , High-Throughput Nucleotide Sequencing , Humans , Mice , Mice, Inbred C57BL , Mutation , Organ Specificity
3.
J Med Virol ; 91(1): 151-154, 2019 01.
Article in English | MEDLINE | ID: mdl-30133759

ABSTRACT

The current study aimed to determine the seroprevalence of hepatitis E virus (HEV) infection among persons who use crack from Midwest region of Brazil. Sera samples from 698 users of crack, collected from November 2013 to July 2015 were tested for anti-HEV immunoglobulin G (IgG) and immunoglobulin M (IgM) markers. Of the 698 serum samples, 99 (14.2%) were positive for anti-HEV IgG. Two samples were positive for anti-HEV IgM but both were negative for HEV RNA. The variables independently associated with anti-HEV positivity were increasing age and absence of stable partnership. This study showed high prevalence of past hepatitis E virus infection among persons who use crack.


Subject(s)
Antibodies, Viral/blood , Crack Cocaine/administration & dosage , Hepatitis E virus/immunology , Hepatitis E/epidemiology , Substance-Related Disorders/complications , Adolescent , Adult , Aged , Brazil/epidemiology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , RNA, Viral/blood , Risk Factors , Seroepidemiologic Studies , Young Adult
4.
Rev Soc Bras Med Trop ; 51(2): 198-202, 2018.
Article in English | MEDLINE | ID: mdl-29768553

ABSTRACT

INTRODUCTION: The prevalence of hepatitis B and hepatitis C and risk behaviors among 402 female sex workers in Central Brazil were investigated by respondent-driven sampling. METHODS: Blood samples were tested for hepatitis B and C markers by enzyme-linked immunosorbent assay. Two hepatitis B vaccination schedules were performed. RESULTS: The prevalence of hepatitis B and C infections were 9.3% and 0.5%, respectively. Susceptibility to hepatitis B infection was observed in 61.5% of subjects. There was no significant difference in adherence index (p=0.52) between vaccination schedules and all participants had protective antibody titers. CONCLUSIONS: This hard-to-reach population requires hepatitis B and C surveillance.


Subject(s)
Hepatitis B/epidemiology , Hepatitis C/epidemiology , Sex Workers/statistics & numerical data , Adolescent , Adult , Brazil/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Hepacivirus/immunology , Hepatitis B/diagnosis , Hepatitis B/prevention & control , Hepatitis B virus/immunology , Hepatitis C/diagnosis , Hepatitis C/prevention & control , Humans , Middle Aged , Prevalence , Risk-Taking , Socioeconomic Factors , Viral Hepatitis Vaccines/administration & dosage , Viral Hepatitis Vaccines/immunology , Young Adult
5.
Rev. Soc. Bras. Med. Trop ; 51(2): 198-202, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-1041449

ABSTRACT

Abstract INTRODUCTION: The prevalence of hepatitis B and hepatitis C and risk behaviors among 402 female sex workers in Central Brazil were investigated by respondent-driven sampling. METHODS: Blood samples were tested for hepatitis B and C markers by enzyme-linked immunosorbent assay. Two hepatitis B vaccination schedules were performed. RESULTS: The prevalence of hepatitis B and C infections were 9.3% and 0.5%, respectively. Susceptibility to hepatitis B infection was observed in 61.5% of subjects. There was no significant difference in adherence index (p=0.52) between vaccination schedules and all participants had protective antibody titers. CONCLUSIONS: This hard-to-reach population requires hepatitis B and C surveillance.


Subject(s)
Humans , Female , Adolescent , Adult , Young Adult , Viral Hepatitis Vaccines/administration & dosage , Hepatitis C/epidemiology , Sex Workers/statistics & numerical data , Hepatitis B/epidemiology , Risk-Taking , Socioeconomic Factors , Brazil/epidemiology , Enzyme-Linked Immunosorbent Assay , Viral Hepatitis Vaccines/immunology , Hepatitis B virus/immunology , Prevalence , Hepatitis C/diagnosis , Hepatitis C/prevention & control , Hepacivirus/immunology , Hepatitis B/diagnosis , Hepatitis B/prevention & control , Middle Aged
6.
Rev Inst Med Trop Sao Paulo ; 59: e87, 2017 Dec 21.
Article in English | MEDLINE | ID: mdl-29267595

ABSTRACT

The purpose of this study was to estimate the prevalence of intestinal parasites in both cooperative-affiliated and independent waste pickers operating at the municipal sanitary landfill in Campo Grande, Mato Grosso do Sul, Brazil, and associate these findings with hemoglobin, eosinophils, vitamin A and C levels and interleukin 5 and 10 (IL-5 and IL-10) production. Biological samples were collected, in addition to clinical, epidemiological, and sociodemographic data. Stool analyzes were based on sedimentation by centrifugation and on spontaneous sedimentation. High-performance liquid chromatography was used to determine vitamin A and C levels. ELISA was employed to quantify interleukins. Intestinal parasites were found in 29 of the 66 subjects assessed (43.9%). Endolimax nana (22.7%), Entamoeba coli (21.1%), Giardia lamblia (6.1%), Entamoeba histolytica/E. dispar (4.5%), and Ascaris lumbricoides (4.5%) were the most prevalent species. Pathogenic parasites were detected in 11 individuals (16.7%). Hypovitaminoses A and C were detected in 19.6% (13/66) and 98.4% (65/66) of subjects, respectively. IL-5 and IL-10 production was observed in 21 (31.8%) and 32 (48.4%) subjects, respectively. Infection with pathogenic intestinal parasites was not a cause of vitamin A and C deficiency or IL-5 and IL-10 production among these workers.


Subject(s)
Intestinal Diseases, Parasitic/epidemiology , Occupational Diseases/epidemiology , Occupational Diseases/parasitology , Waste Disposal Facilities , Adult , Aged , Ascorbic Acid/blood , Brazil/epidemiology , Chromatography, High Pressure Liquid , Enzyme-Linked Immunosorbent Assay , Eosinophils , Feces/parasitology , Female , Hemoglobins/analysis , Humans , Interleukin-10/blood , Interleukin-5/blood , Intestinal Diseases, Parasitic/parasitology , Male , Middle Aged , Prevalence , Social Conditions , Socioeconomic Factors , Vitamin A/blood , Young Adult
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