Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.

Admission COVID-19 clinical risk assessment for guiding patient placement and diagnostic testing strategy.

Introduction: Without universal access to point-of-care SARS-CoV-2 testing, many hospitals rely on clinical judgement alone for identifying cases of COVID-19 early.

Methods: Cambridge University Hospitals NHS Foundation Trust introduced a 'traffic light' clinical judgement aid to the COVID-19 admissions unit in mid-March 2020. Ability to accurately predict COVID-19 was audited retrospectively across different stages of the epidemic.

Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study.

There is an urgent need for rapid SARS-CoV-2 testing in hospitals to limit nosocomial spread. We report an evaluation of point of care (POC) nucleic acid amplification testing (NAAT) in 149 participants with parallel combined nasal and throat swabbing for POC versus standard lab RT-PCR testing. Median time to result is 2.

A novel, sensitive dual-indicator cell line for detection and quantification of inducible, replication-competent latent HIV-1 from reservoir cells.

Understanding the mechanisms involved in HIV infection and latency, and development of a cure, rely on the availability of sensitive research tools such as indicator cells, which allow rigorous quantification of viral activity. Here we describe the construction and validation of a novel dual-indicator cell line, Sup-GGR, which offers two different readouts to quantify viral replication. A construct expressing both Gaussia luciferase and hrGFP in a Tat- and Rev-dependent manner was engineered into SupT1-CCR5 to create Sup-GGR cells.

HIV Silencing and Inducibility Are Heterogeneous and Are Affected by Factors Intrinsic to the Virus.

Transcriptionally silent HIV proviruses form the major obstacle to eradicating HIV. Many studies of HIV latency have focused on the cellular mechanisms that maintain silencing of proviral DNA. Here we show that viral sequence variation affecting replicative ability leads to variable rates of silencing and ability to reactivate.

No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years.

The persistence of infected T cells harbouring intact HIV proviruses is the barrier to the eradication of HIV. This reservoir is stable over long periods of time despite antiretroviral therapy. There has been controversy on whether low level viral replication is occurring at sanctuary sites periodically reseeding infected cells into the latent reservoir to account its durability.

Innovations in the quantitative virus outgrowth assay and its use in clinical trials.

A robust measure of the size of the latent HIV reservoir is essential to quantifying the effect of interventions designed to deplete the pool of reactivatable, replication competent proviruses. In addition to the ability to measure a biologically relevant parameter, any assay designed to be used in a clinical trial needs to be reproducible and scalable. The need to quantify the number of resting CD4+ T cells capable of releasing infectious virus has led to the development of the quantitative viral outgrowth assay (VOA).

A highly reproducible quantitative viral outgrowth assay for the measurement of the replication-competent latent HIV-1 reservoir.

Cure of Human Immunodeficiency Virus (HIV) infection remains elusive due to the persistence of HIV in a latent reservoir. Strategies to eradicate latent infection can only be evaluated with robust, sensitive and specific assays to quantitate reactivatable latent virus. We have taken the standard peripheral blood mononuclear cell (PBMC) based viral outgrowth methodology and from it created a logistically simpler and more highly reproducible assay to quantify replication-competent latent HIV in resting CD4 T cells, both increasing accuracy and decreasing cost and labour.

The genome of the sparganosis tapeworm Spirometra erinaceieuropaei isolated from the biopsy of a migrating brain lesion.

Background: Sparganosis is an infection with a larval Diphyllobothriidea tapeworm. From a rare cerebral case presented at a clinic in the UK, DNA was recovered from a biopsy sample and used to determine the causative species as Spirometra erinaceieuropaei through sequencing of the cox1 gene. From the same DNA, we have produced a draft genome, the first of its kind for this species, and used it to perform a comparative genomics analysis and to investigate known and potential tapeworm drug targets in this tapeworm.

Early development of immune reconstitution inflammatory syndrome related to Pneumocystis pneumonia after antiretroviral therapy.

Immune reconstitution inflammatory syndrome is a recognized complication after the initiation of combination antiretroviral therapy (cART). We report a patient who developed life-threatening pulmonary immune reconstitution inflammatory syndrome (IRIS) three days after initiation of cART. We reviewed published cases of IRIS after Pneumocystis pneumonia (PCP), in particular the time from initiation of cART to IRIS event.

Waking up the sleepers: HIV latency and reactivation.

In a patient infected with HIV-1, the presence of latently infected cells from which the virus can be reactivated and rekindle HIV infection in the patient necessitates lifelong administration of antiretroviral treatment. The biology of HIV latency and viral silencing is now becoming clearer at a molecular and cellular level. However, our understanding of HIV-1 latency in vivo is still inadequate.

Chromatin, gene silencing and HIV latency.

One of the cellular defenses against virus infection is the silencing of viral gene expression. There is evidence that at least two gene-silencing mechanisms are used against the human immuno-deficiency virus (HIV). Paradoxically, this cellular defense mechanism contributes to viral latency and persistence, and we review here the relationship of viral latency to gene-silencing mechanisms.

A method to estimate the efficiency of gene expression from an integrated retroviral vector.

Background: Proviral gene expression is a critical step in the retroviral life cycle and an important determinant in the efficiency of retrovirus based gene therapy vectors. There is as yet no method described that can assess the efficiency of proviral gene expression while vigorously excluding the contribution from unstable species such as passively transferred plasmid and LTR circles. Here, we present a method that can achieve this.

HIV-1 Gag-RNA interaction occurs at a perinuclear/centrosomal site; analysis by confocal microscopy and FRET.

The Gag polyprotein is the major structural protein of human immunodeficiency virus-1 (HIV-1) constituting the viral core. Between translation on cytoplasmic polysomes and assembly into viral particles at the plasma membrane, it specifically captures the RNA genome of the virus through binding RNA structural motifs (packaging signals -Psi) in the RNA. RNA is believed to be a structural facilitator of Gag assembly.