Viral Hepatitis Among African Immigrants with Hepatocellular Carcinoma in Minnesota: High Prevalence Yet Low Awareness.

We aimed to study the virologic profile of immigrants from Africa with viral hepatitis-related hepatocellular carcinoma (HCC) who received care at our institution. We conducted a descriptive study among African-born patients with HCC who received care at University of Minnesota Medical Center from 2011 to 2018. We analyzed the prevalence, virologic profiles and treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections prior to HCC diagnosis.

Aceruloplasminemia: A Case Report and Review of a Rare and Misunderstood Disorder of Iron Accumulation.

Aceruloplasminemia is a rare disorder of iron accumulation inherited in an autosomal recessive fashion. It commonly presents as chronic microcytic anemia, and then progresses to signs and symptoms that are due to the accumulation of iron in multiple organs such as the brain, liver, pancreas, and thyroid. We present an asymptomatic patient with a history of microcytic anemia, who was evaluated for abnormal liver enzymes, and ultimately diagnosed with aceruloplasminemia.

Liver targeted gene therapy: Insights into emerging therapies.

The large number of monogenic metabolic disorders originating in the liver poses a unique opportunity for development of gene therapy modalities to pursue curative approaches. Various disorders have been successfully treated via liver-directed gene therapy, though most of the advances have been in animal models, with only limited success in clinical trials. Pre-clinical data in animals using non-viral approaches, including the Sleeping Beauty transposon system, are discussed.

The Evolution of Gene Therapy in the Treatment of Metabolic Liver Diseases.

Monogenic metabolic disorders of hepatic origin number in the hundreds, and for many, liver transplantation remains the only cure. Liver-targeted gene therapy is an attractive treatment modality for many of these conditions, and there have been significant advances at both the preclinical and clinical stages. Viral vectors, including retroviruses, lentiviruses, adenovirus-based vectors, adeno-associated viruses and simian virus 40, have differing safety, efficacy and immunogenic profiles, and several of these have been used in clinical trials with variable success.

Precision medicine, agriculture, and genome editing: science and ethics.

The era of precision medicine has generated advances in various fields of science and medicine with the potential for a paradigm shift in healthcare delivery that will ultimately lead to an individualized approach to medicine. Such timely topics were explored in 2018 at a workshop held at the Third International Conference on One Medicine One Science (iCOMOS), in Minneapolis, Minnesota. A broad range of scientists and regulatory experts provided detailed insights into the challenges and opportunities associated with precision medicine and gene editing.

"Let my liver rather heat with wine" - a review of hepatic fibrosis pathophysiology and emerging therapeutics.

Cirrhosis is characterized by extensive hepatic fibrosis, and it is the 14th leading cause of death worldwide. Numerous contributing conditions have been implicated in its development, including infectious etiologies, medication overdose or adverse effects, ingestible toxins, autoimmunity, hemochromatosis, Wilson's disease and primary biliary cholangitis to list a few. It is associated with portal hypertension and its stigmata (varices, ascites, hepatic encephalopathy, combined coagulopathy and thrombophilia), and it is a major risk factor for hepatocellular carcinoma.

Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research.

Unlabelled: Eliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 infections are subtype C, and novel antigenic properties have been described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was developed as a research reagent and candidate immunogen.

Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops.

Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3' that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops.

HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner.

Objective: To study the dose-dependent manner of HIV-1 Tat-induced effects on viral replication, internalization and spread, and to directly observe these effects on soluble Env immunogens and virus-like particles.

Design: In order to determine the manner through which Tat affects viral replication, we incubated cells, virions and soluble Env spikes with Tat at different concentrations, and directly visualized the effects of such incubation.

Methods: Cell-based infectivity assays were carried out to assay Tat dose-dependency of viral infectivity.

Putative role of Tat-Env interaction in HIV infection.

Objective: To study the complex formed between Tat protein and Env soluble trimeric immunogen, and compare with previously determined structures of Env native trimers and Env-CD4m complexes.

Design: The soluble Env trimer was used to mimic the spike glycoprotein on the virus surface for the study. To overcome limitations of other structural determination methods, cryoelectron microscopy was employed to image the complex, and single particle reconstruction was utilized to reconstruct the structure of the complex from collected micrographs.

Chimeric hepatitis E virus-like particle as a carrier for oral-delivery.

Oral delivery with virus-like particles (VLPs) is advantageous because of the inherited entry pathway from their parental viral capsids, which enables VLP to withstand the harsh and enzymatic environment associated with human digestive tract. However, the repeat use of this system is challenged by the self-immunity. In order to overcome this problem, we engineered the recombinant capsid protein of hepatitis E virus by inserting p18 peptide, derived from the V3 loop of HIV-1 gp120, into the antibody-binding site.

Quaternary structures of HIV Env immunogen exhibit conformational vicissitudes and interface diminution elicited by ligand binding.

The human immunodeficiency virus envelope protein is the key element mediating entry into host cells. Conformational rearrangement of Env upon binding to the host CD4 receptor and chemokine coreceptor drives membrane fusion. We elucidated the quaternary arrangement of the soluble Env trimeric immunogen o-gp140ΔV2TV1, in both its native (unliganded) and CD4-induced (liganded) states by cryoelectron microscopy and molecular modeling.