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

Author

Chen, Wei-Hung, Hajduczki, Agnes, Martinez, Elizabeth J., Bai, Hongjun, Matz, Hanover, Hill, Thomas M., Lewitus, Eric, Chang, William C., Dawit, Layla, Peterson, Caroline E., Rees, Phyllis A., Ajayi, Adelola B., Golub, Emily S., Swafford, Isabella, Dussupt, Vincent, David, Sapna, Mayer, Sandra V., Soman, Sandrine, Kuklis, Caitlin, Corbitt, Courtney, King, Jocelyn, Choe, Misook, Sankhala, Rajeshwer S., Thomas, Paul V., Zemil, Michelle, Wieczorek, Lindsay, Hart, Tricia, Duso, Debora, Kummer, Larry, Yan, Lianying, Sterling, Spencer L., Laing, Eric D., Broder, Christopher C., Williams, Jazmean K., Davidson, Edgar, Doranz, Benjamin J., Krebs, Shelly J., Polonis, Victoria R., Paquin-Proulx, Dominic, Rolland, Morgane, Reiley, William W., Gromowski, Gregory D., Modjarrad, Kayvon, Dooley, Helen, and Joyce, M. Gordon

Published
2023
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2. Contemporary HIV-1 consensus Env with AI-assisted redesigned hypervariable loops promote antibody binding

Author

Bai, Hongjun, primary, Lewitus, Eric, additional, Li, Yifan, additional, Thomas, Paul V., additional, Zemil, Michelle, additional, Merbah, Mélanie, additional, Peterson, Caroline E., additional, Thuraisamy, Thujitha, additional, Rees, Phyllis A., additional, Hajduczki, Agnes, additional, Dussupt, Vincent, additional, Slike, Bonnie, additional, Mendez-Rivera, Letzibeth, additional, Schmid, Annika, additional, Kavusak, Erin, additional, Rao, Mekhala, additional, Smith, Gabriel, additional, Frey, Jessica, additional, Sims, Alicea, additional, Wieczorek, Lindsay, additional, Polonis, Victoria, additional, Krebs, Shelly J., additional, Ake, Julie A., additional, Vasan, Sandhya, additional, Bolton, Diane L., additional, Joyce, M. Gordon, additional, Townsley, Samantha, additional, and Rolland, Morgane, additional

Published
2024
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6. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States

Author

Wieczorek, Lindsay, primary, Sanders-Buell, Eric, additional, Zemil, Michelle, additional, Lewitus, Eric, additional, Kavusak, Erin, additional, Heller, Jonah, additional, Molnar, Sebastian, additional, Rao, Mekhala, additional, Smith, Gabriel, additional, Bose, Meera, additional, Nguyen, Amy, additional, Dhungana, Adwitiya, additional, Okada, Katherine, additional, Parisi, Kelly, additional, Silas, Daniel, additional, Slike, Bonnie, additional, Ganesan, Anuradha, additional, Okulicz, Jason, additional, Lalani, Tahaniyat, additional, Agan, Brian K., additional, Crowell, Trevor A., additional, Darden, Janice, additional, Rolland, Morgane, additional, Vasan, Sandhya, additional, Ake, Julie, additional, Krebs, Shelly J., additional, Peel, Sheila, additional, Tovanabutra, Sodsai, additional, and Polonis, Victoria R., additional

Published
2023
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7. An Adaptive Threshold in Mammalian Neocortical Evolution

Author

Lewitus, Eric, Kelava, Iva, Kalinka, Alex T., Tomancak, Pavel, and Huttner, Wieland B

Subjects
Quantitative Biology - Populations and Evolution, Quantitative Biology - Neurons and Cognition
Abstract

Expansion of the neocortex is a hallmark of human evolution. However, it remains an open question what adaptive mechanisms facilitated its expansion. Here we show, using gyrencephaly index (GI) and other physiological and life-history data for 102 mammalian species, that gyrencephaly is an ancestral mammalian trait. We provide evidence that the evolution of a highly folded neocortex, as observed in humans, requires the traversal of a threshold of 10^9 neurons, and that species above and below the threshold exhibit a bimodal distribution of physiological and life-history traits, establishing two phenotypic groups. We identify, using discrete mathematical models, proliferative divisions of progenitors in the basal compartment of the developing neocortex as evolutionarily necessary and sufficient for generating a fourteen-fold increase in daily prenatal neuron production and thus traversal of the neuronal threshold. We demonstrate that length of neurogenic period, rather than any novel progenitor-type, is sufficient to distinguish cortical neuron number between species within the same phenotypic group., Comment: Currently under review; 38 pages, 5 Figures, 13 Supplementary Figures, 2 Tables

Published
2013
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18. HIV-1 infections with multiple founders associate with the development of neutralization breadth

Author

Lewitus, Eric, primary, Townsley, Samantha M., additional, Li, Yifan, additional, Donofrio, Gina C., additional, Dearlove, Bethany L., additional, Bai, Hongjun, additional, Sanders-Buell, Eric, additional, O’Sullivan, Anne Marie, additional, Bose, Meera, additional, Kibuuka, Hannah, additional, Maganga, Lucas, additional, Nitayaphan, Sorachai, additional, Sawe, Fredrick K., additional, Eller, Leigh Anne, additional, Michael, Nelson L., additional, Polonis, Victoria R., additional, Ake, Julie A., additional, Vasan, Sandhya, additional, Robb, Merlin L., additional, Tovanabutra, Sodsai, additional, Krebs, Shelly J., additional, and Rolland, Morgane, additional

Published
2022
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20. Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1

Author

Shangguan, Shida, primary, Ehrenberg, Philip K, additional, Geretz, Aviva, additional, Yum, Lauren, additional, Kundu, Gautam, additional, May, Kelly, additional, Fourati, Slim, additional, Nganou-Makamdop, Krystelle, additional, Williams, LaTonya D, additional, Sawant, Sheetal, additional, Lewitus, Eric, additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Chariyalertsak, Suwat, additional, Rerks-Ngarm, Supachai, additional, Rolland, Morgane, additional, Douek, Daniel C, additional, Gilbert, Peter, additional, Tomaras, Georgia D, additional, Michael, Nelson L, additional, Vasan, Sandhya, additional, and Thomas, Rasmi, additional

Published
2021
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21. Author response: Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1

Author

Shangguan, Shida, primary, Ehrenberg, Philip K, additional, Geretz, Aviva, additional, Yum, Lauren, additional, Kundu, Gautam, additional, May, Kelly, additional, Fourati, Slim, additional, Nganou-Makamdop, Krystelle, additional, Williams, LaTonya D, additional, Sawant, Sheetal, additional, Lewitus, Eric, additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Chariyalertsak, Suwat, additional, Rerks-Ngarm, Supachai, additional, Rolland, Morgane, additional, Douek, Daniel C, additional, Gilbert, Peter, additional, Tomaras, Georgia D, additional, Michael, Nelson L, additional, Vasan, Sandhya, additional, and Thomas, Rasmi, additional

Published
2021
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22. RV144 vaccine imprinting constrained HIV-1 evolution following breakthrough infection

Author

Lewitus, Eric, primary, Sanders-Buell, Eric, additional, Bose, Meera, additional, O’Sullivan, Anne Marie, additional, Poltavee, Kultida, additional, Li, Yifan, additional, Bai, Hongjun, additional, Mdluli, Thembi, additional, Donofrio, Gina, additional, Slike, Bonnie, additional, Zhao, Hong, additional, Wong, Kim, additional, Chen, Lennie, additional, Miller, Shana, additional, Lee, Jenica, additional, Ahani, Bahar, additional, Lepore, Steven, additional, Muhammad, Sevan, additional, Grande, Rebecca, additional, Tran, Ursula, additional, Dussupt, Vincent, additional, Mendez-Rivera, Letzibeth, additional, Nitayaphan, Sorachai, additional, Kaewkungwal, Jaranit, additional, Pitisuttithum, Punnee, additional, Rerks-Ngarm, Supachai, additional, O’Connell, Robert J, additional, Janes, Holly, additional, Gilbert, Peter B, additional, Gramzinski, Robert, additional, Vasan, Sandhya, additional, Robb, Merlin L, additional, Michael, Nelson L, additional, Krebs, Shelly J, additional, Herbeck, Joshua T, additional, Edlefsen, Paul T, additional, Mullins, James I, additional, Kim, Jerome H, additional, Tovanabutra, Sodsai, additional, and Rolland, Morgane, additional

Published
2021
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24. Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as the primary mechanism of vaccine-induced protection against HIV-1

Author

Shangguan, Shida, primary, Ehrenberg, Philip K., additional, Geretz, Aviva, additional, Yum, Lauren, additional, Kundu, Gautam, additional, May, Kelly, additional, Fourati, Slim, additional, Nganou-Makamdop, Krystelle, additional, Williams, LaTonya D., additional, Sawant, Sheetal, additional, Lewitus, Eric, additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Chariyalertsak, Suwat, additional, Rerks-Ngarm, Supachai, additional, Rolland, Morgane, additional, Douek, Daniel, additional, Gilbert, Peter, additional, Tomaras, Georgia D., additional, Michael, Nelson, additional, Vasan, Sandhya, additional, and Thomas, Rasmi, additional

Published
2021
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28. Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1.

Author

Shida Shangguan, Ehrenberg, Philip K., Geretz, Aviva, Yum, Lauren, Kundu, Gautam, May, Kelly, Fourati, Slim, Nganou-Makamdop, Krystelle, Williams, LaTonya D., Sawant, Sheetal, Lewitus, Eric, Pitisuttithum, Punnee, Sorachai Nitayaphan, Suwat Chariyalertsak, Supachai Rerks-Ngarm, Rolland, Morgane, Douek, Daniel C., Gilbert, Peter, Tomaras, Georgia D., and Michael, Nelson L.

Published
2021
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31. Factors influencing estimates of HIV-1 infection timing using BEAST.

Author

Dearlove, Bethany, Tovanabutra, Sodsai, Owen, Christopher L., Lewitus, Eric, Li, Yifan, Sanders-Buell, Eric, Bose, Meera, O'Sullivan, Anne-Marie, Kijak, Gustavo, Miller, Shana, Poltavee, Kultida, Lee, Jenica, Bonar, Lydia, Harbolick, Elizabeth, Ahani, Bahar, Pham, Phuc, Kibuuka, Hannah, Maganga, Lucas, Nitayaphan, Sorachai, and Sawe, Fred K.

Subjects
HIV, MOLECULAR clock, GENES, BAYESIAN analysis, TIME management, INFECTION
Abstract

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. We analyzed HIV-1 sequences sampled one week, one month and six months after HIV-1 diagnosis in 39 individuals. We found that shared diversity and temporal signal was limited in acute infection, and insufficient to allow timing inferences in the shortest HIV-1 genes, thus dated phylogenies were primarily analyzed for env, gag, pol and near full-length genomes. There was no one best fitting model across participants and genes, though relaxed molecular clocks (73% of best fitting models) and the Bayesian skyline (49%) tended to be favored. For infections with single founders, the infection date was estimated to be around one week pre-diagnosis for env (IQR: 3–9 days) and gag (IQR: 5–9 days), whilst the genome placed it at a median of 10 days (IQR: 4–19). Multiply-founded infections proved problematic to date. Our ability to compare timing inferences to precise estimates of HIV-1 infection (within a week) highlights that molecular dating methods can be applied to within-host datasets from early infection. Nonetheless, our results also suggest caution when using uniform clock and population models or short genes with limited information content. Author summary: Molecular dating using phylogenetics allows us to estimate the date of an infection from time-stamped within-host sequences alone. There are large datasets of HIV-1 sequences, but genome and gene analyses are not often performed in parallel and rarely with the possibility to compare results against a known narrow window of infection. We showed that all but the longest genes are near-clonal in acute infection, with little information for dating purposes. For infections with single founders, we estimated the eclipse phase—the time between HIV-1 exposure and the first positive diagnostic test—to last between one and two weeks using env, gag, pol and near full-length genomes. This approach could be used to narrow the date of suspected infection in ongoing clinical trials for the prevention of HIV-1 infection. [ABSTRACT FROM AUTHOR]

Published
2021
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32. 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.

Author

Rolland, Morgane, Tovanabutra, Sodsai, Dearlove, Bethany, Li, Yifan, Owen, Christopher L., Lewitus, Eric, Sanders-Buell, Eric, Bose, Meera, O'Sullivan, AnneMarie, Rossenkhan, Raabya, Labuschagne, Jan Phillipus Lourens, Edlefsen, Paul T., Reeves, Daniel B., Kijak, Gustavo, Miller, Shana, Poltavee, Kultida, Lee, Jenica, Bonar, Lydia, Harbolick, Elizabeth, and Ahani, Bahar

Subjects
HAMMING distance, PEAK load, PATHOLOGY, ADULTS, VIRAL load, ECLIPSES
Abstract

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. We sequenced 1,280 HIV-1 genomes from 39 participants at a median of 4, 32 and 170 days post-diagnosis. HIV-1 infections were dated by using sequence-based methods and a viral load regression method. Bayesian coalescent and viral load regression estimated that infections occurred a median of 6 days prior to diagnosis (IQR: 9–3 and 11–4 days prior, respectively). Poisson-Fitter, which analyzes the distribution of hamming distances among sequences, estimated a median of 7 days prior to diagnosis (IQR: 15–4 days) based on sequences sampled 4 days post-diagnosis, but it did not yield plausible results using sequences sampled at 32 days. Fourteen participants reported a high-risk exposure event at a median of 8 days prior to diagnosis (IQR: 12 to 6 days prior). These different methods concurred that HIV-1 infection occurred about a week before detectable viremia, corresponding to 20 days (IQR: 34–15 days) before peak viral load. Together, our methods comparison helps define a framework for future dating studies in early HIV-1 infection. Author summary: HIV-1 infected individuals rarely know when they became infected but knowing when an infection occurred provides critical information regarding HIV-1 pathogenesis and epidemiology. Using a unique cohort in which infection was known to have occurred in a narrow interval, we investigated methods to estimate the timing of infections. Several methods suggested that HIV-1 infection typically occurs a median of one week before the infection can be detected by HIV-1 RNA testing. Going forward, we provide a strategy that can be used to elucidate the origin of an acute/early infection. [ABSTRACT FROM AUTHOR]

Published
2020
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35. Neurodevelopmental LincRNA Microsyteny Conservation and Mammalian Brain Size Evolution

Author

Lewitus, Eric and Huttner, Wieland B.

Subjects
Mammals, Brain Mapping, Genome, Sequence Analysis, RNA, Gene Expression Profiling, lcsh:R, Brain, Computational Biology, lcsh:Medicine, Genomics, Organ Size, Biological Evolution, Evolution, Molecular, Mice, Animals, Humans, Regression Analysis, RNA, Long Noncoding, lcsh:Q, lcsh:Science, Conserved Sequence, Research Article, Transcription Factors
Abstract

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. Using published fetal human RNA-seq data, we show that the gene-neighborhood (i.e., microsynteny) of long intergenic non-coding RNAs (lincRNAs) implicated in cortical development is differentially conserved in large-brained species, lending support to the hypothesis that lincRNAs regulating neurogenesis are selectively lost in small-brained species. We provide evidence that this is not a phenomenon attributable to lincRNA expressed in all tissue types and is therefore likely to represent an adaptive function in the evolution of neurogenesis. A strong correlation between transcription factor-adjacency and lincRNA sequence conservation reinforces this conclusion.

Published
2015

40. Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development

Author

Huttner, Wieland B., Lewitus, Eric, and Kelava, Iva

Subjects
Mammals, gyrencephaly, Subventricular zone, extracellular matrix, mammals, neocortex, neural progenitors, phylogenetics, subventricular zone, Neocortex, Hypothesis and Theory Article, Extracellular Matrix, lcsh:RC321-571, ddc:610, Biologie, Genetik, Säugetiere, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Neuroscience
Abstract

There is a basic rule to mammalian neocortical expansion: as it expands, so does it fold. The degree to which it folds, however, cannot strictly be attributed to its expansion. Across species, cortical volume does not keep pace with cortical surface area, but rather folds appear more rapidly than expected. As a result, larger brains quickly become disproportionately more convoluted than smaller brains. Both the absence (lissencephaly) and presence (gyrencephaly) of cortical folds is observed in all mammalian orders and, while there is likely some phylogenetic signature to the evolutionary appearance of gyri and sulci, there are undoubtedly universal trends to the acquisition of folds in an expanding neocortex. Whether these trends are governed by conical expansion of neocortical germinal zones, the distribution of cortical connectivity, or a combination of growth- and connectivity-driven forces remains an open question. But the importance of cortical folding for evolution of the uniquely mammalian neocortex, as well as for the incidence of neuropathologies in humans, is undisputed. In this hypothesis and theory article, we will summarize the development of cortical folds in the neocortex, consider the relative influence of growth- versus connectivity-driven forces for the acquisition of cortical folds between and within species, assess the genetic, cell-biological, and mechanistic implications for neocortical expansion, and discuss the significance of these implications for human evolution, development, and disease. We will argue that evolutionary increases in the density of neuron production, achieved via maintenance of a basal proliferative niche in the neocortical germinal zones, drive the conical migration of neurons towards the cortical surface and ultimately lead to the establishment of cortical folds in large-brained mammal species.

Published
2013

41. Neocortical development as an evolutionary platform for intragenomic conflict

Author

Lewitus, Eric and Kalinka, Alex T.

Subjects
X-chromosome, Mammals, Genomic Imprinting, evolution, non-coding RNA, Neocortex, lcsh:Human anatomy, development, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, parent-offspring conflict, Neuroscience, lcsh:RC321-571, lcsh:QM1-695
Abstract

Embryonic development in mammals has evolved a platform for genomic conflict between mothers and embryos and, by extension, between maternal and paternal genomes. The evolutionary interests of the mother and embryo may be maximized through the promotion of sex-chromosome genes and imprinted alleles, resulting in the rapid evolution of postzygotic phenotypes preferential to either the maternal or paternal genome. In eutherian mammals, extraordinary in utero maternal investment in the brain, and neocortex especially, suggests that convergent evolution of an expanded mammalian neocortex along divergent lineages may be explained, in part, by parent-of-origin-linked gene expression arising from parent-offspring conflict. The influence of this conflict on neocortical development and evolution, however, has not been investigated at the genomic level. In this hypothesis and theory article, we provide preliminary evidence for positive selection in humans in the regions of two platforms of intragenomic conflict – chromosomes 15q11-q13 and X – and explore the potential relevance of cis-regulated imprinted domains to neocortical expansion in mammalian evolution. We present the hypothesis that maternal- and paternal-specific pressures on the developing neocortex compete intragenomically to influence neocortical expansion in mammalian evolution.

Published
2013

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