Attacking HIV-1 RNA versus DNA by sequence-specific approaches: RNAi versus CRISPR-Cas.

Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection.

The hepatitis C virus nonstructural protein 3 Q80K polymorphism is frequently detected and transmitted among HIV-infected MSM in the Netherlands.

Objectives: The Q80K polymorphism is a naturally occurring resistance-associated variant in the hepatitis C virus (HCV) nonstructural protein 3 (NS3) region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks.

Design And Methods: Stored blood samples from HCV genotype 1a-infected patients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny.

Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria.

Antimicrobial peptides (AMPs) have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the membrane is the sole target of AMPs. Progress has been made in clarifying the possible targets of these peptides, which is reported in this review with as focus gram-positive vegetative cells and spores.

Atypical Porcine Pestivirus: A Possible Cause of Congenital Tremor Type A-II in Newborn Piglets.

Congenital tremor type A-II in piglets has been regarded as a transmissible disease since the 1970s, possibly caused by a very recently-described virus: atypical porcine pestivirus (APPV). Here, we describe several strains of APPV in piglets with clinical signs of congenital tremor (10 of 10 farms tested). Piglets on a farm with no history of congenital tremor were PCR-negative for the virus.

Clinical Presentations and Epidemiology of Urinary Tract Infections.

Urinary tract infection (UTI) is one of the most common bacterial infections, and the incidence in women is much higher than in men. The diagnosis of a UTI can be made based on a combination of symptoms and a positive urine analysis or culture. Most UTIs are uncomplicated UTIs, defined as cystitis in a woman who is not pregnant, is not immunocompromised, has no anatomical and functional abnormalities of the urogenital tract, and does not exhibit signs of tissue invasion and systemic infection.

A Novel Astrovirus-Like RNA Virus Detected in Human Stool.

Several novel clades of astroviruses have recently been identified in human faecal samples. Here, we describe a novel astrovirus-like RNA virus detected in human stools, which we have tentatively named bastrovirus. The genome of this novel virus consists of 6,300 nucleotides organized in three open reading frames.

Therapeutic Administration of a Monoclonal Anti-Il-1β Antibody Protects Against Experimental Melioidosis.

Background: Melioidosis, caused by the gram-negative bacterium Burkholderia pseudomallei, is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia. The NLRP3 inflammasome and its downstream product interleukin-1 beta (IL-1β) have been proposed to play crucial roles in melioidosis. In this study, we characterized the role of IL-1β more closely and we assessed its therapeutic potential.

A prospective study of the importance of enteric fever as a cause of non-malarial febrile illness in patients admitted to Chittagong Medical College Hospital, Bangladesh.

Background: Fever is a common cause of hospital admission in Bangladesh but causative agents, other than malaria, are not routinely investigated. Enteric fever is thought to be common.

Methods: Adults and children admitted to Chittagong Medical College Hospital with a temperature of ≥38.

Time to clearance of Chlamydia trachomatis RNA and DNA after treatment in patients coinfected with Neisseria gonorrhoeae - a prospective cohort study.

Background: Performing a test of cure (TOC) could demonstrate success or failure of antimicrobial treatment of Chlamydia trachomatis infection, but recommendations for the timing of a TOC using nucleic acid amplification tests (NAATs) are inconsistent. We assessed time to clearance of C. trachomatis after treatment, using modern RNA- and DNA-based NAATs.

Impact of HIV infection on the presentation, outcome and host response in patients admitted to the intensive care unit with sepsis; a case control study.

Background: Sepsis is a prominent reason for intensive care unit (ICU) admission in patients with HIV. We aimed to investigate the impact of HIV infection on presentation, outcome and host response in sepsis.

Methods: We performed a prospective observational study in the ICUs of two tertiary hospitals.

Cigarette Smoking and Inflammation, Monocyte Activation, and Coagulation in HIV-Infected Individuals Receiving Antiretroviral Therapy, Compared With Uninfected Individuals.

Smoking may affect cardiovascular disease risk more strongly in human immunodeficiency virus (HIV)-infected individuals than HIV-uninfected individuals. We hypothesized that an interaction at the level of the immune system may contribute to this increased risk. We assessed soluble markers of inflammation (high-sensitivity C-reactive protein [hsCRP]), immune activation (soluble [s]CD14 and sCD163), and coagulation (D-dimer) in HIV-infected and uninfected never, former, and current smokers.

Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome.

Cost-effectiveness analysis of pre-exposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study.

Background: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. Unfortunately, PrEP is not reimbursed in most European countries.

A cross-sectional study on the concordance between vaginal HPV DNA detection and type-specific antibodies in a multi-ethnic cohort of women from Amsterdam, the Netherlands - the HELIUS study.

Background: Acquisition of genital human papillomavirus (HPV) infection is common among the young, sexually active population. Genital HPV infections do not always lead to seroconversion. We aimed to assess the association between cervico-vaginal high risk (hr) HPV DNA and type-specific antibodies in an ethnically diverse cohort of young women.

HIV-1 Escape from a Peptidic Anchor Inhibitor through Stabilization of the Envelope Glycoprotein Spike.

Unlabelled: The trimeric HIV-1 envelope glycoprotein spike (Env) mediates viral entry into cells by using a spring-loaded mechanism that allows for the controlled insertion of the Env fusion peptide into the target membrane, followed by membrane fusion. Env is the focus of vaccine research aimed at inducing protective immunity by antibodies as well as efforts to develop drugs that inhibit the viral entry process. The molecular factors contributing to Env stability and decay need to be understood better in order to optimally design vaccines and therapeutics.

Natural infection as a blueprint for rational HIV vaccine design.

So far, the development of a human immunodeficiency virus (HIV) vaccine has been unsuccessful. However, recent progress in the field of broadly neutralizing antibodies (bNAbs) has reinvigorated the search for an HIV vaccine. bNAbs develop in a minority of HIV infected individuals and passive transfer of these bNAbs to non-human primates provides protection from HIV infection.

Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

Objectives: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients.

Methods: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions.

Historical Trends in the Hepatitis C Virus Epidemics in North America and Australia.

Background:  Bayesian evolutionary analysis (coalescent analysis) based on genetic sequences has been used to describe the origins and spread of rapidly mutating RNA viruses, such as influenza, Ebola, human immunodeficiency virus (HIV), and hepatitis C virus (HCV).

Methods:  Full-length subtype 1a and 3a sequences from early HCV infections from the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3), as well as from public databases from a time window of 1977-2012, were used in a coalescent analysis with BEAST software to estimate the origin and progression of the HCV epidemics in Australia and North America. Convergent temporal trends were sought via independent epidemiological modeling.

Linkage to HIV care before and after the introduction of provider-initiated testing and counselling in six Rwandan health facilities.

HIV testing and counselling forms the gateway to the HIV care and treatment continuum. Therefore, the World Health Organization recommends provider-initiated testing and counselling (PITC) in countries with a generalized HIV epidemic. Few studies have investigated linkage-to-HIV-care among out-patients after PITC.

Impact of the biased nucleotide composition of viral RNA genomes on RNA structure and codon usage.

We are interested in the influence of nucleotide composition on the fundamental characteristics of the virus RNA genome. Most RNA viruses have genomes with a distinct nucleotide composition, e.g.

Difference in Aortic Stiffness Between Treated Middle-Aged HIV Type 1-Infected and Uninfected Individuals Largely Explained by Traditional Cardiovascular Risk Factors, With an Additional Contribution of Prior Advanced Immunodeficiency.

Background: Patients with HIV, even with suppressed viremia on combination antiretroviral therapy, are at increased risk for cardiovascular disease. The underlying pathophysiology remains to be clarified. Aortic stiffness, known to be associated with cardiovascular disease in the general population, was investigated in a cohort of HIV type 1 (HIV 1)-infected and similar but uninfected individuals.

Cost-Effectiveness of Dual Antimicrobial Therapy for Gonococcal Infections Among Men Who Have Sex With Men in the Netherlands.

Background: In response to the rising threat of resistance to first-line antibiotics for gonorrhea, international guidelines recommend dual antimicrobial therapy. However, some countries continue to recommend monotherapy. We assess the cost-effectiveness of dual therapy with ceftriaxone and azithromycin compared with monotherapy with ceftriaxone, for control of gonorrhea among men who have sex with men in the Netherlands.

Design of the FemCure study: prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care.

Background: In women, anorectal infections with Chlamydia trachomatis (CT) are about as common as genital CT, yet the anorectal site remains largely untested in routine care. Anorectal CT frequently co-occurs with genital CT and may thus often be treated co-incidentally. Nevertheless, post-treatment detection of CT at both anatomic sites has been demonstrated.

From clinical sample to complete genome: Comparing methods for the extraction of HIV-1 RNA for high-throughput deep sequencing.

The BEEHIVE (Bridging the Evolution and Epidemiology of HIV in Europe) project aims to analyse nearly-complete viral genomes from >3000 HIV-1 infected Europeans using high-throughput deep sequencing techniques to investigate the virus genetic contribution to virulence. Following the development of a computational pipeline, including a new de novo assembler for RNA virus genomes, to generate larger contiguous sequences (contigs) from the abundance of short sequence reads that characterise the data, another area that determines genome sequencing success is the quality and quantity of the input RNA. A pilot experiment with 125 patient plasma samples was performed to investigate the optimal method for isolation of HIV-1 viral RNA for long amplicon genome sequencing.