A Symphony of Destruction: Dynamic Differential Fibrinogenolytic Toxicity by Rattlesnake (Crotalus and Sistrurus) Venoms
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This study adopts rattlesnakes as a model group to investigate the evolutionary history of venom coagulotoxicity in the context of phylogenetics, natural history, and biology. Venom-induced clotting of human plasma and fibrinogen was determined and mapped onto the rattlesnake phylogenetic tree to reconstruct the evolution of coagulotoxicity across the group. Results indicate that venom phenotype is often independent of phylogenetic relationships in rattlesnakes, suggesting the importance of diet and/or other environmental variables.
In Vitro and In Vivo Functions of SARS-CoV-2 Infection-Enhancing and Neutralizing Antibodies
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Antibody-dependent enhancement of infection is a concern for clinical use of antibodies. Researchers isolated neutralizing antibodies against the receptor-binding domain (RBD) or N-terminal domain (NTD) of SARS-CoV-2 spike from COVID-19 patients. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific binding modes. RBD and NTD antibodies mediated both neutralization and infection enhancement in vitro.
Antibody-Based CCR5 Blockade Protects Macaques From Mucosal SHIV Transmission
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The efficacy of antiretroviral therapy (ART) as pre-exposure prophylaxis against HIV is hindered by incomplete patient adherence and ART-resistant variants. Researchers found that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges with a CCR5-tropic simian-human immunodeficiency virus (SHIVSF162P3). Biweekly injection of Leronlimab at 50 mg/kg provided complete protection from SHIV infection.
Psychosocial Stress Alters the Immune Response and Results in Higher Viral Load During Acute SIV Infection in a Pigtailed Macaque Model of HIV
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Social distancing is an important countermeasure for a pandemic, but social isolation may also have adverse health outcomes in the context of infectious diseases, such as HIV. Researchers compared commonly measured parameters of HIV progression between singly and socially housed simian immunodeficiency virus (SIV)-infected pigtailed macaques.
Characterization of Axolotl Lampbrush Chromosomes by Fluorescence In Situ Hybridization and Immunostaining
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The lampbrush chromosomes (LBCs) in oocytes of the Mexican axolotl (Ambystoma mexicanum) were identified by their relative lengths and predicted centromeres; they have never been associated completely with the mitotic karyotype, linkage maps, or genome assembly. The authors identified 9 of the axolotl LBCs using RNA sequencing to identify actively transcribed genes and 13 bacterial artificial clone probes containing pieces of active genes.
The Giant Axolotl Genome Uncovers the Evolution, Scaling, and Transcriptional Control of Complex Gene Loci
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Vertebrates harbor recognizably orthologous gene complements but vary 100-fold in genome size. How chromosomal organization scales with genome expansion is unclear, and how acute changes in gene regulation, as during axolotl limb regeneration, occur in the context of a vast genome has remained a riddle. Here, Schloissnig et al. describe the chromosome-scale assembly of the giant, 32 Gb axolotl genome. Hi-C contact data revealed the scaling properties of interphase and mitotic chromosome organization.
Rhesus Macaques Build New Social Connections After a Natural Disaster
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Climate change has increased the frequency and intensity of weather-related disasters such as hurricanes and floods. In 2017, Puerto Rico suffered its worst natural disaster, Hurricane Maria, leaving 3,000 dead and provoking a mental health crisis. Cayo Santiago Island, home to a population of rhesus macaques (Macaca mulatta), was devastated by this storm. Testard et al. compared social networks of two groups of macaques before and after the hurricane and found an increase in affiliative social connections, driven largely by monkeys most socially isolated before Hurricane Maria.
A Platform for Experimental Precision Medicine: The Extended BXD Mouse Family
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Systems genetics using rodent models has recently been revitalized thanks to several resources: the BXD family, the Hybrid Mouse Diversity Panel, and the Collaborative Cross. The main limitation has been modest mapping power and precision due to small strain numbers. Investigators expanded the BXD family of mice to 140 fully isogenic strains. Heritable traits can be mapped with precision. Current BXD phenomes include much omics data and thousands of quantitative traits.
New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention, and Cure
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Researchers knew that substitution of HIV-1 Env residue 375-serine by aromatic residues enhances binding to rhesus CD4 enabling primary HIV-1 Envs to support replication as simian-human immunodeficiency virus (SHIV) chimeras in rhesus monkeys. The investigators constructed SHIVs containing 10 primary Envs corresponding to HIV-1 subtypes A, B, C, AE, and AG. Only one with histidine at Env375 replicated efficiently in rhesus cells. Replacement of wild-type Env375 residues by tryptophan, tyrosine, phenylalanine, or histidine in the other 9 SHIVs led to efficient replication.
SARS-CoV-2 Induces Robust Germinal Center CD4 T Follicular Helper Cell Responses in Rhesus Macaques
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SARS-CoV-2 infection in both sexes of rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating CD4 T follicular helper (Tfh) cells, which are critical for persistent antibody responses. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. This skewing is important to note, as weak interferon responses observed in COVID patients could hamper effective antiviral antibody and CD8 T-cell responses.