Plasma virome and the risk of blood-borne infection in persons with substance use disorder.

There is an urgent need for innovative methods to reduce transmission of bloodborne pathogens like HIV and HCV among people who inject drugs (PWID). We investigate if PWID who acquire non-pathogenic bloodborne viruses like anelloviruses and pegiviruses might be at greater risk of acquiring a bloodborne pathogen. PWID who later acquire HCV accumulate more non-pathogenic viruses in plasma than matched controls who do not acquire HCV infection.

SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood.

Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.

SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood from the San Francisco Bay Area.

We report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.

Author Correction: Development and performance of prototype serologic and molecular tests for hepatitis delta infection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Early emergence of anti-HCV antibody implicates donor origin in recipients of an HCV-infected organ.

Hepatitis C virus (HCV) seroconversion among HCV-uninfected transplant recipients from HCV-infected (NAT+/Antibody+) or HCV-exposed (NAT-/Antibody+) donors has been reported. However, the origin of anti-HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV-uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti-HCV antibody (both IgG and IgM isotypes).

Identification of a putative novel genotype 3/rabbit hepatitis E virus (HEV) recombinant.

Hepatitis E virus (HEV) is a viral pathogen transmitted by the fecal-oral route and is a major cause of waterborne acute hepatitis in many developing countries. In addition to infecting humans, HEV has been identified in swine, wild boars, rabbits and other mammals; with swine and wild boars being main reservoirs for zoonotic transmission of HEV. There are four major HEV genotypes known to infect humans; genotypes 1 (HEV-1) and 2 (HEV-2) are restricted to humans, and genotypes 3 (HEV-3) and 4 (HEV-4) are zoonotic.

Hepatitis C virus surveillance and identification of human pegivirus 2 in a large Cameroonian cohort.

The prevalence of chronic hepatitis C virus (HCV) and the presence of human pegivirus 2 (HPgV-2) have not been examined in Cameroon, although HCV has been associated with HPgV-2 infections previously. Herein we aimed to characterize the burden and genetic diversity of HCV and the presence of HPgV-2 in Cameroon. Retrospective plasma specimens collected from N = 12 369 consenting subjects in South Cameroon from 2013 to 2016 were included in the study.

Performance Evaluation of a Prototype Architect Antibody Assay for Babesia microti.

The tick-borne protozoan is responsible for more than 200 cases of transfusion-transmitted babesiosis (TTB) infection in the United States that have occurred over the last 30 years. Measures to mitigate the risk of TTB include nucleic acid testing (NAT) and antibody testing. A fully automated prototype antibody test was developed on the Architect instrument.

Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process.

Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms.

Development and performance of prototype serologic and molecular tests for hepatitis delta infection.

Worldwide, an estimated 5% of hepatitis B virus (HBV) infected people are coinfected with hepatitis delta virus (HDV). HDV infection leads to increased mortality over HBV mono-infection, yet HDV diagnostics are not widely available. Prototype molecular (RNA) and serologic (IgG) assays were developed for high-throughput testing on the Abbott m2000 and ARCHITECT systems, respectively.

Development of a high-throughput multiplexed real time RT-PCR assay for detection of human pegivirus 1 and 2.

Human Pegivirus 2 (HPgV-2) was recently identified in the bloodstream of HCV-infected and multiply transfused individuals. Initial reports show HPgV-2 circulates at a low prevalence in HCV co-infected individuals, necessitating testing of large cohorts of samples to identify infected persons. The identification of additional HPgV-2 cases was facilitated by the development of a high throughput and reliable molecular reverse transcription polymerase chain reaction (RT-PCR) assay intended for use on the automated Abbott m2000 system with a capability of extracting and testing 96 samples at once.

Antibodies to the Novel Human Pegivirus 2 Are Associated with Active and Resolved Infections.

A novel blood-borne human pegivirus (HPgV), HPgV-2, was recently identified in hepatitis C virus (HCV)-infected individuals and individuals who had received multiple transfusions. Robust serological assays capable of detecting antibodies in HPgV-2-infected individuals are needed to establish global seroprevalence rates and potential disease associations. The two objectives of this study were to determine the utility of mammalian cell-expressed HPgV-2 E2 glycoprotein or bacterium-expressed nonstructural protein 4AB (NS4AB) in detecting past or present infections and to compare the total prevalence (antibody and RNA positive) of HPgV-2 with that of the other human pegivirus, HPgV-1 (GB virus C [GBV-C]).

Role of Serologic and Molecular Diagnostic Assays in Identification and Management of Hepatitis C Virus Infection.

The drugs available for the treatment of hepatitis C virus (HCV) have evolved to provide shorter treatment duration and higher rates of sustained virologic response (SVR), and the role of HCV infection diagnostic tests has had to evolve in order to meet changing clinical needs. This review gives an overview on the role of HCV infection diagnostic testing (molecular and serological tools) used in the diagnosis and management of HCV infection. All of this critical information guides physician decisions to optimize patient clinical outcomes.

Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection.

Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2), by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares <32% amino acid identity.

Molecular determinants and dynamics of hepatitis C virus secretion.

The current model of hepatitis C virus (HCV) production involves the assembly of virions on or near the surface of lipid droplets, envelopment at the ER in association with components of VLDL synthesis, and egress via the secretory pathway. However, the cellular requirements for and a mechanistic understanding of HCV secretion are incomplete at best. We combined an RNA interference (RNAi) analysis of host factors for infectious HCV secretion with the development of live cell imaging of HCV core trafficking to gain a detailed understanding of HCV egress.

The kinase activity of pseudorabies virus US3 is required for modulation of the actin cytoskeleton.

Different viruses exploit the host cytoskeleton to facilitate replication and spread. The conserved US3 protein of the alphaherpesvirus pseudorabies virus induces actin stress fiber disassembly and formation of actin-containing cell projections, which are associated with enhanced intercellular virus spread. Proteins of members of other virus families, notably vaccinia virus F11L protein and human immunodeficiency virus Nef protein, induce actin rearrangements that are very similar to those induced by US3.

Two viral kinases are required for sustained long distance axon transport of a neuroinvasive herpesvirus.

Axonal transport is essential for the successful establishment of neuroinvasive herpesvirus infections in peripheral ganglia (retrograde transport) and the subsequent spread to exposed body surfaces following reactivation from latency (anterograde transport). We examined two components of pseudorabies virus (US3 and UL13), both of which are protein kinases, as potential regulators of axon transport. Following replication of mutant viruses lacking kinase activity, newly assembled capsids displayed an increase in retrograde motion that prevented efficient delivery of capsids to the distal axon.

The capsid and tegument of the alphaherpesviruses are linked by an interaction between the UL25 and VP1/2 proteins.

How alphaherpesvirus capsids acquire tegument proteins remains a key question in viral assembly. Using pseudorabies virus (PRV), we have previously shown that the 62 carboxy-terminal amino acids of the VP1/2 large tegument protein are essential for viral propagation and when transiently expressed as a fusion to green fluorescent protein relocalize to nuclear capsid assemblons following viral infection. Here, we show that localization of the VP1/2 capsid-binding domain (VP1/2cbd) into assemblons is conserved in herpes simplex virus type 1 (HSV-1) and that this recruitment is specifically on capsids.

Targeting of herpesvirus capsid transport in axons is coupled to association with specific sets of tegument proteins.

The capsids of neurotropic herpesviruses have the remarkable ability to move in specific directions within axons. By modulating bidirectional capsid transport to favor either retrograde (minus-end) or anterograde (plus-end) motion, these viruses travel to sensory ganglia or peripheral tissue at specific stages of infection. By using correlative motion analysis to simultaneously monitor the trafficking of distinct viral proteins in living neurons, we demonstrate that viral "tegument" proteins are complexed to capsids moving in axons.