Newly emerged hantaviruses replicate primarily in the pulmonary endothelium, cause acute platelet loss, and result hantavirus syndrome (HPS). We now report that specific integrins expressed on platelets endothelial cells permit cellular entry of HPS-associated hantaviruses. Infection with hantaviruses, NY-1 Sin Nombre virus (SNV), is inhibited by antibodies to β 3 -integrin ligand, vitronectin. In contrast, infection nonpathogenic (no associated human disease) Prospect Hill was fibronectin 1...

ABSTRACT Dengue virus (DENV) replication is inhibited by the prior addition of type I interferon or RIG-I agonists that elicit RIG-I/MAVS/TBK1/IRF3-dependent protective responses. DENV infection primary human endothelial cells (ECs) results in a rapid increase viral titer, which suggests inhibits replication-restrictive RIG-I/interferon beta (IFN-β) induction pathways within ECs. Our findings demonstrate serotype 4 (DENV4) nonstructural (NS) proteins NS2A and NS4B RIG-I-, MDA5-, MAVS-,...

ABSTRACT Hantaviruses replicate primarily in the vascular endothelium and cause two human diseases, hemorrhagic fever with renal syndrome (HFRS) hantavirus pulmonary (HPS). In this report, we demonstrate that cellular entry of HFRS-associated hantaviruses is facilitated by specific integrins expressed on platelets, endothelial cells, macrophages. Infection umbilical vein cells Vero E6 HFRS-causing Hantaan (HTN), Seoul (SEO), Puumala (PUU) inhibited antibodies to α v β 3 integrin ligand...

The complete gene 4 nucleotide sequence was determined for rhesus rotavirus and each of 11 viral variants selected by neutralizing monoclonal antibodies. Gene is 2362 bases in length encodes a protein, VP3, 776 amino acids with calculated Mr 86,500. A conserved trypsin cleavage site, located at acid 247, divides VP3 into VP8 VP5. Neutralizing antibodies directed were used to select that escaped neutralization. Each variant contains single mutation permits growth the presence antibody....

Hantaviruses cause two human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary (HPS). infect endothelial cells but little or no damage to the infected endothelium. We analyzed Affymetrix DNA Arrays (Santa Clara, CA) cell transcriptional responses directed by hantaviruses associated HPS [New York-1 virus (NY-1V)], HFRS [Hantaan (HTNV)], a not disease [Prospect Hill (PHV)]. Hantavirus infections induced 117 cellular genes repressed 25 >3-fold, 4 days...

Hantaviruses infect human endothelial cells and cause two vascular permeability-based diseases: hemorrhagic fever with renal syndrome hantavirus pulmonary syndrome. Hantavirus infection alone does not permeabilize cell monolayers. However, pathogenic hantaviruses inhibit the function of alphav beta3 integrins on cells, disease permeability deficits are consequences dysfunctional that normally regulate permeabilizing growth factor (VEGF) responses. Here we show Hantaan, Andes, New York-1...

Zika virus (ZIKV) is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in Americas. ZIKV uniquely persists human bodily fluids for up to 6 months, sexually transmitted, traverses placenta blood-brain barrier (BBB) damage neurons. Cells support persistent replication mechanisms by which establishes persistence remain enigmatic but central entry into protected neuronal compartments. The endothelial cell (EC) lining capillaries normally...

SARS-CoV-2 infects pulmonary epithelial cells through ACE2 receptors and causes ARDS. COVID-19 progressive respiratory failure resulting from diffuse alveolar damage systemic coagulopathy, thrombosis, capillary inflammation that tie responses to EC dysfunction.

ABSTRACT Dengue virus causes leakage of the vascular endothelium, resulting in dengue hemorrhagic fever and shock syndrome. The endothelial cell lining vasculature regulates capillary permeability is altered by immune chemokine responses which affect fluid barrier functions endothelium. Our findings indicate that human cells are highly susceptible to infection (type 4). We found productively infects ∼80% primary cells, rapid release ∼10 5 virions 1 day postinfection. Analysis potential...

Integrins alpha2beta1, alphaXbeta2, and alphaVbeta3 have been implicated in rotavirus cell attachment entry. The virus spike protein VP4 contains the alpha2beta1 ligand sequence DGE at amino acid positions 308 to 310, outer capsid VP7 alphaXbeta2 GPR. To determine viral proteins sequences involved define roles of alphaVbeta3, we analyzed ability rotaviruses their reassortants use these integrins for binding infection effect peptides DGEA GPRP on events. Many laboratory-adapted human, monkey,...

The amino-terminal trypsin cleavage fragment of VP4, called VP8, was expressed from a recombinant baculovirus in Sf-9 cells. baculovirus-expressed VP8 protein is antigenically conserved as demonstrated by its recognition library neutralizing monoclonal antibodies. In cell sonicates, the capable agglutinating human type 0 erythrocytes, indicating that functionally intact rhesus rotavirus viral hemagglutinin contained 247-amino acid fragment. Amino similarities between and 282 amino acids...

Sera from infants and adults who received a live, attenuated monovalent rotavirus vaccine of serotype 1, 2, 3, or 4 VP7 specificity rhesus (RRV) VP4 were analyzed for serotype-specific antibody responses by an epitope blocking immunoassay (EBA) neutralization. Although the assays correlated well, to individual neutralization proteins different defined antigenic sites on same protein could be distinguished only EBA. In general, adult vaccinees exhibited both homotypic response immunizing...

ABSTRACT Hantaviruses cause two diseases with prominent vascular permeability defects, hemorrhagic fever renal syndrome and hantavirus pulmonary syndrome. All hantaviruses infect human endothelial cells, although it is unclear what differentiates pathogenic from nonpathogenic hantaviruses. We observed dramatic differences in interferon-specific transcriptional responses between at 1 day postinfection, suggesting that pathogenesis may part be determined by viral regulation of cellular...

Hantavirus infections are noted for their ability to infect endothelial cells, cause acute thrombocytopenia, and trigger 2 vascular-permeability-based diseases. However, hantavirus not lytic, the mechanisms by which hantaviruses capillary permeability thrombocytopenia only partially understood. The role of beta(3) integrins in hemostasis inactivation integrin receptors pathogenic suggest involvement altered platelet cell functions that regulate permeability. Here, we determined bind...

Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and shock syndrome (DSS). Preexisting antibodies to virus disposes patients immune-enhanced edema (DSS) or disease following infection by a discrete serotype. Although the endothelium is primary barrier, direct effects of on endothelial cells (ECs) have not been considered factors in pathogenesis. Here, we show human ECs elicits immune-enhancing EC responses. Our results...

Abstract Rotavirus is the most important worldwide cause of severe gastroenteritis in infants and young children. Intestinal epithelial cells are principal targets rotavirus infection, but response enterocytes to infection largely unknown. We determined that HT-29 intestinal results prompt activation NF-κB (<2 h), STAT1, ISG F3 (3 h). Genetically inactivated virus-like particles assembled from baculovirus-expressed viral proteins also activated NF-κB. induced mRNA for several C-C...

The complete M segment sequences of hantaviruses amplified from tissues a patient with hantavirus pulmonary syndrome in the northeastern United States and white-footed mice, Peromyscus leucopus, New York were 99% identical differed those Four Corners virus by 23%. serum this failed to recognize conserved, immunodominant epitope G1 glycoprotein. Collectively, these findings indicate that P. leucopus harbors genetically antigenically distinct causes syndrome.

A murine model was used to determine whether neutralizing monoclonal antibodies (MAbs) with heterotypic specificity directed VP7 (MAb 57-8) or the VP8 fragment of VP4 M14) passively protect mice against challenge various strains rotavirus. (The gene 4 product, an outer capsid protein, has traditionally been called VP3. It proposed, however, that rotavirus product be named VP4. The 3 a core identified recently and VP3 [M. Liu, P. A. Offit, M. K. Estes, Virology 163:28-32, 1988]). Suckling...