The Zika virus NS5 protein binds HSP90 to suppress EGF-induced Akt signaling and trophoblast cell migration.

Zika virus (ZIKV) infection during pregnancy can cause congenital Zika virus syndrome (CZV), including fetal growth restriction and death. In the developing placenta, trophoblast cells respond to epidermal growth factor (EGF) to migrate into the decidua to facilitate implantation and fetal development. EGF activates the Akt protein kinase, a master regulator of trophoblast cell migration.

Cellular RNA interacts with MAVS to promote antiviral signaling.

Antiviral signaling downstream of RIG-I-like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral signaling protein (MAVS). Protein complex function can be modulated by RNA molecules that provide allosteric regulation or act as molecular guides or scaffolds. We hypothesized that RNA plays a role in organizing MAVS signaling platforms.

Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids.

Long-chain acyl-CoA synthetase 1 (ACSL1) catalyzes the conversion of long-chain fatty acids to acyl-CoAs. ACSL1 is required for β-oxidation in tissues that rely on fatty acids as fuel, but no consensus exists on why ACSL1 is induced by inflammatory mediators in immune cells. We used a comprehensive and unbiased approach to investigate the role of ACSL1 induction by interferon type I (IFN-I) in myeloid cells in vitro and in a mouse model of IFN-I overproduction.

Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients.

: The chikungunya virus (CHIKV), transmitted by infected Aedes mosquitoes, has caused a significant number of infections worldwide. In Brazil, the emergence of the CHIKV-ECSA genotype in 2014 posed a major public health challenge due to its association with more severe symptoms. : This study aimed to shed new light on the host immune response by examining the whole-blood transcriptomic profile of both CHIKV-acute and chronically infected individuals from Feira de Santana, Bahia, Brazil, a region heavily affected by CHIKV, Dengue, and Zika virus epidemics.

The Human Neural Cell Atlas of Zika Infection in developing human brain tissue: viral pathogenesis, innate immunity, and lineage reprogramming.

Zika virus (ZIKV) infection during pregnancy can lead to fetal brain infection and developmental anomalies collectively known as congenital Zika syndrome (CZS). To define the molecular features underlying CZS in a relevant human cell model, we evaluated ZIKV infection and neurodevelopment in primary fetal brain explants and induced pluripotent stem cell-derived mixed neural cultures at single cell resolution. We identified astrocytes as key innate immune sentinel cells detecting ZIKV and producing IFN-β.

Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.

CD4-mediated immunity shapes neutrophil-driven tuberculous pathology.

Pulmonary (Mtb) infection results in highly heterogeneous lesions ranging from granulomas with central necrosis to those primarily comprised of alveolitis. While alveolitis has been associated with prior immunity in human post-mortem studies, the drivers of these distinct pathologic outcomes are poorly understood. Here, we show that these divergent lesion structures can be modeled in C3HeB/FeJ mice and are regulated by prior immunity.

scPathoQuant: a tool for efficient alignment and quantification of pathogen sequence reads from 10× single cell sequencing datasets.

Motivation: Currently there is a lack of efficient computational pipelines/tools for conducting simultaneous genome mapping of pathogen-derived and host reads from single cell RNA sequencing (scRNAseq) output from pathogen-infected cells. Contemporary options include processes involving multiple steps and/or running multiple computational tools, increasing user operations time.

Results: To address the need for new tools to directly map and quantify pathogen and host sequence reads from within an infected cell from scRNAseq datasets in a single operation, we have built a python package, called scPathoQuant.

Pre-challenge gut microbial signature predicts RhCMV/SIV vaccine efficacy in rhesus macaques.

Background: RhCMV/SIV vaccines protect ∼59% of vaccinated rhesus macaques against repeated limiting-dose intra-rectal exposure with highly pathogenic SIVmac239M, but the exact mechanism responsible for the vaccine efficacy is not known. It is becoming evident that complex interactions exist between gut microbiota and the host immune system. Here we aimed to investigate if the rhesus gut microbiome impacts RhCMV/SIV vaccine-induced protection.

CELLULAR RNA INTERACTS WITH MAVS TO PROMOTE ANTIVIRAL SIGNALING.

Immune signaling needs to be well-regulated to promote clearance of pathogens, while preventing aberrant inflammation. Interferons (IFNs) and antiviral genes are activated by the detection of viral RNA by RIG-I-like receptors (RLRs). Signal transduction downstream of RLRs proceeds through a multi-protein complex organized around the central adaptor protein MAVS.

Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys.

Remdesivir is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 () into lung cells, thereby forming the bioactive triphosphate . , an analog of ATP, inhibits the SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription of viral RNA. Strong clinical results for have prompted interest in oral approaches to generate .

Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques.

Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. IFNmod treatment in uninfected RMs was observed to induce a modest up-regulation of only antiviral IFN-stimulated genes (ISGs); however, in SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs.

Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1).

Background: Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19.

Methods: Swab samples were collected at baseline and longitudinally through day 29.

Innate immunity and interferon in SARS-CoV-2 infection outcome.

Innate immunity and the actions of type I and III interferons (IFNs) are essential for protection from SARS-CoV-2 and COVID-19. Each is induced in response to infection and serves to restrict viral replication and spread while directing the polarization and modulation of the adaptive immune response. Owing to the distribution of their specific receptors, type I and III IFNs, respectively, impart systemic and local actions.

Evaluation of the immunogenicity and efficacy of an rVSV vaccine against Zika virus infection in macaca nemestrina.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes an acute febrile illness. ZIKV can be transmitted between sexual partners and from mother to fetus. Infection is strongly associated with neurologic complications in adults, including Guillain-Barré syndrome and myelitis, and congenital ZIKV infection can result in fetal injury and congenital Zika syndrome (CZS).

Rapid Antigen and Antibody Microfluidic Immunofluorescence Assays Compared to Culture, PCR, and Laboratory Reference Tests: Performance in a Longitudinal Cohort.

We evaluated the performance of rapid antigen (RAg) and antibody (RAb) microfluidic diagnostics with serial sampling of 71 participants at 6 visits over 2 months following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Rapid tests showed strong agreement with laboratory references (κAg = 81.0%; κAb = 87.