Transcriptional programming mediated by the histone demethylase KDM5C regulates dendritic cell population heterogeneity and function.

Functional and phenotypic heterogeneity of dendritic cells (DCs) play crucial roles in facilitating the development of diverse immune responses essential for host protection. Here, we report that KDM5C, a histone lysine demethylase, regulates conventional or classical DC (cDC) and plasmacytoid DC (pDC) population heterogeneity and function. Mice deficient in KDM5C in DCs have increased proportions of cDC2Bs and cDC1s, which is partly dependent on type I interferon (IFN) and pDCs.

LKB1 controls inflammatory potential through CRTC2-dependent histone acetylation.

Deregulated inflammation is a critical feature driving the progression of tumors harboring mutations in the liver kinase B1 (LKB1), yet the mechanisms linking LKB1 mutations to deregulated inflammation remain undefined. Here, we identify deregulated signaling by CREB-regulated transcription coactivator 2 (CRTC2) as an epigenetic driver of inflammatory potential downstream of LKB1 loss. We demonstrate that LKB1 mutations sensitize both transformed and non-transformed cells to diverse inflammatory stimuli, promoting heightened cytokine and chemokine production.

Dependence on a variable residue limits the breadth of an HIV MPER neutralizing antibody, despite convergent evolution with broadly neutralizing antibodies.

Broadly neutralizing antibodies (bNAbs) that target the membrane-proximal external region (MPER) of HIV gp41 envelope, such as 4E10, VRC42.01 and PGZL1, can neutralize >80% of viruses. These three MPER-directed monoclonal antibodies share germline antibody genes (IGHV1-69 and IGKV3-20) and form a bNAb epitope class.

SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay.

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020.

SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay.

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020.

Advancing HIV Vaccine Research With Low-Cost High-Performance Computing Infrastructure: An Alternative Approach for Resource-Limited Settings.

Next-generation sequencing (NGS) technologies have revolutionized biological research by generating genomic data that were once unaffordable by traditional first-generation sequencing technologies. These sequencing methodologies provide an opportunity for in-depth analyses of host and pathogen genomes as they are able to sequence millions of templates at a time. However, these large datasets can only be efficiently explored using bioinformatics analyses requiring huge data storage and computational resources adapted for high-performance processing.

Evidence for both Intermittent and Persistent Compartmentalization of HIV-1 in the Female Genital Tract.

HIV-1 has been shown to evolve independently in different anatomical compartments, but studies in the female genital tract have been inconclusive. Here, we examined evidence of compartmentalization using HIV-1 subtype C envelope (Env) glycoprotein genes (gp160) obtained from matched cervicovaginal lavage (CVL) and plasma samples over 2 to 3 years of infection. HIV-1 gp160 amplification from CVL was achieved for only 4 of 18 acutely infected women, and this was associated with the presence of proinflammatory cytokines and/or measurable viremia in the CVL.

Positive Selection at Key Residues in the HIV Envelope Distinguishes Broad and Strain-Specific Plasma Neutralizing Antibodies.

The development of HIV broadly neutralizing antibodies (bNAbs) has previously been shown to be associated with viral evolution and high levels of genetic diversity in the HIV envelope (Env) glycoprotein. However, few studies have examined Env evolution in those who fail to develop neutralization breadth in order to assess whether bNAbs result from distinct evolutionary pathways. We compared Env evolution in eight HIV-1-infected participants who developed bNAbs to six donors with similar viral loads who did not develop bNAbs over three years of infection.

V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time.

The global distribution of reveals little evidence for frequent recent, human-mediated long distance dispersal events.

(BBTV; family Nanoviridae, genus ) is a multi-component single-stranded DNA virus, which infects banana plants in many regions of the world, often resulting in large-scale crop losses. We analyzed 171 banana leaf samples from fourteen countries and recovered, cloned, and sequenced 855 complete BBTV components including ninety-four full genomes. Importantly, full genomes were determined from eight countries, where previously no full genomes were available (Samoa, Burundi, Republic of Congo, Democratic Republic of Congo, Egypt, Indonesia, the Philippines, and the USA [HI]).

Ongoing geographical spread of Tomato yellow leaf curl virus.

Tomato yellow leaf curl virus (TYLCV) seriously impacts tomato production throughout tropical and sub-tropical regions of the world. It has a broad geographical distribution and continues to spread to new regions in the Indian and Pacific Oceans including Australia, New Caledonia and Mauritius. We undertook a temporally-scaled, phylogeographic analysis of all publicly available, full genome sequences of TYLCV, together with 70 new genome sequences from Australia, Iran and Mauritius.

Divergent evolutionary and epidemiological dynamics of cassava mosaic geminiviruses in Madagascar.

Background: Cassava mosaic disease (CMD) in Madagascar is caused by a complex of at least six African cassava mosaic geminivirus (CMG) species. This provides a rare opportunity for a comparative study of the evolutionary and epidemiological dynamics of distinct pathogenic crop-infecting viral species that coexist within the same environment. The genetic and spatial structure of CMG populations in Madagascar was studied and Bayesian phylogeographic modelling was applied to infer the origins of Madagascan CMG populations within the epidemiological context of related populations situated on mainland Africa and other south western Indian Ocean (SWIO) islands.

Accessing carboxylesterase diversity from termite hindgut symbionts through metagenomics.

A shotgun metagenomic library was constructed from termite hindgut symbionts and subsequently screened for esterase activities. A total of 68 recombinant clones conferring esterolytic phenotypes were identified, of which the 14 most active were subcloned and sequenced. The nucleotide lengths of the esterase-encoding open reading frames (ORFs) ranged from 783 to 2,592 bp and encoded proteins with predicted molecular masses of between 28.