Contemporary HIV-1 consensus Env with AI-assisted redesigned hypervariable loops promote antibody binding.

An effective HIV-1 vaccine must elicit broadly neutralizing antibodies (bnAbs) against highly diverse Envelope glycoproteins (Env). Since Env with the longest hypervariable (HV) loops is more resistant to the cognate bnAbs than Env with shorter HV loops, we redesigned hypervariable loops for updated Env consensus sequences of subtypes B and C and CRF01_AE. Using modeling with AlphaFold2, we reduced the length of V1, V2, and V5 HV loops while maintaining the integrity of the Env structure and glycan shield, and modified the V4 HV loop.

HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s.

Unlabelled: Knowledge of HIV-1 global sequence diversity is critical for developing an effective prophylactic against HIV-1 infection. We developed the Hervé platform to analyze and visualize trends in HIV-1 diversification. Using Hervé, we analyzed 4,830 Env, 4,407 Gag, and 3,002 Pol publicly available independent sequences corresponding to subtypes A1, A6, B, C, D, F1, and G and circulating recombinant forms (CRFs) 01_AE, 02_AG, and 07_BC; sequences were sampled between 1980 and 2020 from 82 countries.

Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States.

Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa.

Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity.

Despite rapid and ongoing vaccine and therapeutic development, SARS-CoV-2 continues to evolve and evade, presenting a need for next-generation diverse therapeutic modalities. Here we show that nurse sharks immunized with SARS-CoV-2 recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit a set of new antigen receptor antibody (IgNAR) molecules that target two non-overlapping conserved epitopes on the spike RBD. Representative shark antibody variable NAR-Fc chimeras (ShAbs) targeting either of the two epitopes mediate cell-effector functions, with high affinity to all SARS-CoV-2 viral variants of concern, including the divergent Omicron strains.

Design of a pan-betacoronavirus vaccine candidate through a phylogenetically informed approach.

Coronaviruses are a diverse family of viruses that crossed over into humans at least seven times, precipitating mild to catastrophic outcomes. The severe acute respiratory syndrome coronavirus 2 pandemic renewed efforts to identify strains with zoonotic potential and to develop pan-coronavirus vaccines. The analysis of 2181 coronavirus genomes (from 102 host species) confirmed the limited sequence conservation across genera (alpha-, beta-, delta-, and gammacoronavirus) and proteins.

Optimal sequence-based design for multi-antigen HIV-1 vaccines using minimally distant antigens.

The immense global diversity of HIV-1 is a significant obstacle to developing a safe and effective vaccine. We recently showed that infections established with multiple founder variants are associated with the development of neutralization breadth years later. We propose a novel vaccine design strategy that integrates the variability observed in acute HIV-1 infections with multiple founder variants.

Does HIV-1 virulence matter in the ART era?

Are highly virulent HIV-1 strains circulating? Wymant et al. described the first concrete example of a virulent HIV-1 strain associated with high viremia and fast CD4 T cell decline. This is certainly not an isolated case, emphasizing the need for thorough HIV-1 surveillance and universal access to treatment.

HIV-1 infections with multiple founders associate with the development of neutralization breadth.

Eliciting broadly neutralizing antibodies (bnAbs) is a cornerstone of HIV-1 vaccine strategies. Comparing HIV-1 envelope (env) sequences from the first weeks of infection to the breadth of antibody responses observed several years after infection can help define viral features critical to vaccine design. We investigated the relationship between HIV-1 env genetics and the development of neutralization breadth in 70 individuals enrolled in a prospective acute HIV-1 cohort.

Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1.

A gene signature was previously found to be correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus and simian-human immunodeficiency virus challenge models in non-human primates. In this report, we investigated the presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanisms of protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial, which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection.

RV144 vaccine imprinting constrained HIV-1 evolution following breakthrough infection.

The scale of the HIV-1 epidemic underscores the need for a vaccine. The multitude of circulating HIV-1 strains together with HIV-1's high evolvability hints that HIV-1 could adapt to a future vaccine. Here, we wanted to investigate the effect of vaccination on the evolution of the virus post-breakthrough infection.

Factors influencing estimates of HIV-1 infection timing using BEAST.

While large datasets of HIV-1 sequences are increasingly being generated, many studies rely on a single gene or fragment of the genome and few comparative studies across genes have been done. We performed genome-based and gene-specific Bayesian phylogenetic analyses to investigate how certain factors impact estimates of the infection dates in an acute HIV-1 infection cohort, RV217. In this cohort, HIV-1 diagnosis corresponded to the first RNA positive test and occurred a median of four days after the last negative test, allowing us to compare timing estimates using BEAST to a narrow window of infection.

A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants.

The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based.

Molecular dating and viral load growth rates suggested that the eclipse phase lasted about a week in HIV-1 infected adults in East Africa and Thailand.

Most HIV-1 infected individuals do not know their infection dates. Precise infection timing is crucial information for studies that document transmission networks or drug levels at infection. To improve infection timing, we used the prospective RV217 cohort where the window when plasma viremia becomes detectable is narrow: the last negative visit occurred a median of four days before the first detectable HIV-1 viremia with an RNA test, referred below as diagnosis.

A non-parametric analytic framework for within-host viral phylogenies and a test for HIV-1 founder multiplicity.

Phylogenetics is a powerful tool for understanding the diversification dynamics of viral pathogens. Here we present an extension of the spectral density profile of the modified graph Laplacian, which facilitates the characterization of within-host molecular evolution of viruses and the direct comparison of diversification dynamics between hosts. This approach is non-parametric and therefore fast and model-free.

Characterizing and Comparing Phylogenetic Trait Data from Their Normalized Laplacian Spectrum.

The dissection of the mode and tempo of phenotypic evolution is integral to our understanding of global biodiversity. Our ability to infer patterns of phenotypes across phylogenetic clades is essential to how we infer the macroevolutionary processes governing those patterns. Many methods are already available for fitting models of phenotypic evolution to data.

Author Correction: Clade-specific diversification dynamics of marine diatoms since the Jurassic.

In the version of this Article originally published, the authors did not give credit to David G. Mann for the four microscopic images used in Fig. 1a.

Clade-specific diversification dynamics of marine diatoms since the Jurassic.

Diatoms are one of the most abundant and diverse groups of phytoplankton and play a major role in marine ecosystems and the Earth's biogeochemical cycles. Here we combine DNA metabarcoding data from the Tara Oceans expedition with palaeoenvironmental data and phylogenetic models of diversification to analyse the diversity dynamics of marine diatoms. We reveal a primary effect of variation in carbon dioxide partial pressure (pCO) on early diatom diversification, followed by a major burst of diversification in the late Eocene epoch, after which diversification is chiefly affected by sea level, an influx of silica availability and competition with other planktonic groups.

Inferring Evolutionary Process From Neuroanatomical Data.

Brain evolution has interested neuroanatomists for over a century. These interests often fall on how free the brain is to evolve independently of the body, how free brain regions are to evolve independently of each other, and how different environmental and ecological factors affect the brain over evolutionary time. But despite major advances in phylogenetic methods, comparative neuroanatomists have tended to limit their macroevolutionary toolbox to regression-based analyses and ignored the scope of evolutionary process-based models at their disposal.

Detecting Environment-Dependent Diversification From Phylogenies: A Simulation Study and Some Empirical Illustrations.

Understanding the relative influence of various abiotic and biotic variables on diversification dynamics is a major goal of macroevolutionary studies. Recently, phylogenetic approaches have been developed that make it possible to estimate the role of various environmental variables on diversification using time-calibrated species trees, paleoenvironmental data, and maximum-likelihood techniques. These approaches have been effectively employed to estimate how speciation and extinction rates vary with key abiotic variables, such as temperature and sea level, and we can anticipate that they will be increasingly used in the future.

Natural Constraints to Species Diversification.

Identifying modes of species diversification is fundamental to our understanding of how biodiversity changes over evolutionary time. Diversification modes are captured in species phylogenies, but characterizing the landscape of diversification has been limited by the analytical tools available for directly comparing phylogenetic trees of groups of organisms. Here, we use a novel, non-parametric approach and 214 family-level phylogenies of vertebrates representing over 500 million years of evolution to identify major diversification modes, to characterize phylogenetic space, and to evaluate the bounds and central tendencies of species diversification.

Comment on "Cortical folding scales universally with surface area and thickness, not number of neurons".

Mota and Herculano-Houzel (Reports, 3 July 2015, p. 74) assign power functions to neuroanatomical data and present a model to account for evolutionary patterns of cortical folding in the mammalian brain. We detail how the model assumptions are in conflict with experimental and observational work and show that the model itself does not accurately fit the data.

Characterizing and Comparing Phylogenies from their Laplacian Spectrum.

Phylogenetic trees are central to many areas of biology, ranging from population genetics and epidemiology to microbiology, ecology, and macroevolution. The ability to summarize properties of trees, compare different trees, and identify distinct modes of division within trees is essential to all these research areas. But despite wide-ranging applications, there currently exists no common, comprehensive framework for such analyses.

Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.

Cerebral organoids-3D cultures of human cerebral tissue derived from pluripotent stem cells-have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex.

Neurodevelopmental LincRNA Microsyteny Conservation and Mammalian Brain Size Evolution.

The mammalian neocortex has undergone repeated selection for increases and decreases in size and complexity, often over relatively short evolutionary time. But because probing developmental mechanisms across many species is experimentally unfeasible, it is unknown whether convergent morphologies in distantly related species are regulated by conserved developmental programs. In this work, we have taken advantage of the abundance of available mammalian genomes to find evidence of selection on genomic regions putatively regulating neurogenesis in large- versus small-brained species.