Hepatic and pulmonary macrophage activity in a mucosal challenge model of Ebola virus disease.

Background: The inflammatory macrophage response contributes to severe Ebola virus disease, with liver and lung injury in humans.

Objective: We sought to further define the activation status of hepatic and pulmonary macrophage populations in Ebola virus disease.

Methods: We compared liver and lung tissue from terminal Ebola virus (EBOV)-infected and uninfected control cynomolgus macaques challenged via the conjunctival route.

A cross-sectional study of avian influenza A virus in Myanmar live bird markets: Detection of a newly introduced H9N2?

Background: Zoonotic influenza surveillance in Myanmar is sparse, despite the risks of introduction of such viruses from neighboring countries that could impact the poultry industry and lead to spillover to humans.

Methods: In July and August 2019, our multi-institutional partnership conducted a One Health-oriented, cross-sectional surveillance (weekly for 3 weeks) for influenza A and influenza D viruses at the three largest live bird markets in Yangon, Myanmar.

Results: The 27 bioaerosols, 90 bird cage swabs, 90 bird oropharyngeals, and 90 human nasopharyngeal samples yielded molecular influenza A detections in 8 bioaerosols (30.

Macrophage infection, activation, and histopathological findings in ebolavirus infection.

Macrophages contribute to Ebola virus disease through their susceptibility to direct infection, their multi-faceted response to ebolaviruses, and their association with pathological findings in tissues throughout the body. Viral attachment and entry factors, as well as the more recently described influence of cell polarization, shape macrophage susceptibility to direct infection. Moreover, the study of Toll-like receptor 4 and the RIG-I-like receptor pathway in the macrophage response to ebolaviruses highlight important immune signaling pathways contributing to the breadth of macrophage responses.

Cutting-Edge Platforms for Analysis of Immune Cells in the Hepatic Microenvironment-Focus on Tumor-Associated Macrophages in Hepatocellular Carcinoma.

The role of tumor-associated macrophages (TAMs) in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. Most studies rely on platforms that remove intrahepatic macrophages from the microenvironment prior to evaluation. Cell isolation causes activation and phenotypic changes that may not represent their actual biology and function in situ.

Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever.

Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R) mouse model.

Comparison of liver biopsies before and after direct-acting antiviral therapy for hepatitis C and correlation with clinical outcome.

Direct-acting antivirals (DAA) have replaced interferon (IFN)-based therapies for hepatitis C virus. In this retrospective clinical study, we examined differences in histopathologic features in paired liver biopsies collected from the same patient before and after DAA and correlated these findings with clinical outcome. Biopsies (n = 19) were evaluated by quantitative imaging analysis to measure steatosis and fibrosis.

Preclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen.

The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues of the HIV-1-fusion peptide (FP8) - when conjugated to the carrier protein, keyhole limpet hemocyanin (KLH) - to be capable of inducing broadly neutralizing responses against HIV-1 in animal models. However, KLH is a multi-subunit particle derived from a natural source, and its manufacture as a clinical product remains a challenge.

Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens.

Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (24 monomers or 8 trimers) of a single antigen. Here, we design two-component ferritin variants that allow the attachment of two different antigens on a single particle in a defined ratio and geometric pattern.

Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.

While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques.

Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity.

The HIV-1 envelope (Env) trimer is a target for vaccine design as well as a conformational machine that facilitates virus entry by transitioning between prefusion-closed, CD4-bound, and coreceptor-bound conformations by transitioning into a postfusion state. Vaccine designers have sought to restrict the conformation of the HIV-1 Env trimer to its prefusion-closed state as this state is recognized by most broadly neutralizing, but not nonneutralizing, antibodies. We previously identified a disulfide bond, I201C-A433C (DS), which stabilizes Env in the vaccine-desired prefusion-closed state.