Locations of three repetitive sequence families found in BALB/c adult β-globin clones

Three different repeat sequences have been mapped within the cloned EcoRI fragments that Contain the adult β-globin genes from the BALB/c (Hd

Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C’) activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78–88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C’ functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIVSF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy

Recommendations for the design and use of standard virus panels to assess neutralizing antibody responses elicited by candidate Human Immunodeficiency Virus Type 1 vaccines.

Guest commentary.No abstract available

Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques

Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches

AminoTrack TM: Automating the Entry and Analysis of Mutations in Multiple Protein Sequences Using a Spreadsheet Format

AminoTrack TM is a web based tool designed to increase the efficiency with which sequence data is recorded for further analysis. The main purpose of AminoTrack TM is to streamline the process and reduce human error in the identification of mutations present in multiple sequences compared to a reference sequence. Aligned protein sequences are entered in the web submission form and comma delimited files are generated in a zip file for loading into a spreadsheet. These files can be imported into any spreadsheet program that recognizes comma delimited files such as Microsoft Excel or SPSS. The sequences are analyzed for mutations in amino acids, charge changes, and potential N-linked glycosylation sites (PNG). The data may be viewed in a spreadsheet in a columnar binary format of “0 ” and “1 ” with one amino acid position per column. Currently this program is being used to identify mutations in viral proteins as these proteins evolve during infection

The Infectious Molecular Clone and Pseudotyped Virus Models of Human Immunodeficiency Virus Type 1 Exhibit Significant Differences in Virion Composition with Only Moderate Differences in Infectivity and Inhibition Sensitivity ▿

Two frequently employed methods for generating well-characterized, genetically defined infectious human immunodeficiency virus type 1 in vitro include the use of infectious molecular clones (IMCs) and pseudoviruses (PVs) competent for single-round infection. We compared six matched pairs of IMCs and PVs. The relative amounts of Env incorporated and efficiency of cleavage differed substantially between the two systems. Altering the ratio of proviral genome and env expression plasmids can produce pseudovirions that are structurally more similar to the matched IMCs. Differences in Env incorporation and cleavage translated into moderate differences in assays infectivity and sensitivity to neutralizing antibodies and entry inhibitors

ACTIVating Resources for the COVID-19 Pandemic: In Vivo Models for Vaccines and Therapeutics.

The Preclinical Working Group of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership spearheaded by the National Institutes of Health, has been charged with identifying, prioritizing, and communicating SARS-CoV-2 preclinical resources. Reviewing SARS-CoV-2 animal model data facilitates standardization and harmonization and informs knowledge gaps and prioritization of limited resources. To date, mouse, hamster, ferret, guinea pig, and non-human primates have been investigated. Several species are permissive for SARS-CoV-2 replication, often exhibiting mild disease with resolution, reflecting most human COVID-19 cases. More severe disease develops in a few models, some associated with advanced age, a risk factor for human disease. This review provides a snapshot that recommends the suitability of models for testing vaccines and therapeutics, which may evolve as our understanding of COVID-19 disease biology improves. COVID-19 is a complex disease, and individual models recapitulate certain aspects of disease; therefore, the coordination and assessment of animal models is imperative