Hyaluronidase-2 and Its Role as a Cell-Entry Receptor for Sheep Retroviruses That Cause Contagious Respiratory Tract Cancers

2009 ◽  
pp. 407-418
Author(s):  
A. Dusty Miller
Keyword(s):  
Respiratory Tract ◽  
Cell Entry ◽  
A Cell ◽  
Entry Receptor ◽  
Hyaluronidase 2

scholarly journals Ability of Hyaluronidase 2 To Degrade Extracellular Hyaluronan Is Not Required for Its Function as a Receptor for Jaagsiekte Sheep Retrovirus

2007 ◽  
Vol 81 (7) ◽  
pp. 3124-3129 ◽  
Author(s):  
Vladimir Vigdorovich ◽  
A. Dusty Miller ◽  
Roland K. Strong
Keyword(s):  
Recombinant Baculovirus ◽  
Weak Acid ◽  
Cell Entry ◽  
Jaagsiekte Sheep Retrovirus ◽  
Hyaluronidase Activity ◽  
A Cell ◽  
Affinity Interaction ◽  
Entry Receptor ◽  
Inactivating Mutations ◽  
Hyaluronidase 2

ABSTRACT Jaagsiekte sheep retrovirus (JSRV) uses hyaluronidase 2 (Hyal2) as a cell entry receptor. By making inactivating mutations to the catalytic residues of human Hyal2, we found that hyaluronidase activity was dispensable for its receptor function. The affinities of the JSRV envelope glycoprotein for Hyal2 and the Hyal2 mutant were similar, and hyaluronan did not block either high-affinity interaction or virus infection. While generating the Hyal2 mutant, we discovered that our previous analysis of the hyaluronidase activity of Hyal2 was affected by a contaminating hyaluronan lyase, which we have identified as the occlusion-derived baculovirus E66 protein of the recombinant baculovirus used to produce Hyal2. We now report that purified human Hyal2 is a weak acid-active hyaluronidase.

scholarly journals ACE2, TMPRSS2 and L-SIGN expression in placentae from HIV-positive pregnancies exposed to antiretroviral therapy–implications for SARS-CoV-2 placental infection

2021 ◽  
Author(s):  
Smriti Kala ◽  
Ksenia Meteleva ◽  
Lena Serghides
Keyword(s):  
Antiretroviral Therapy ◽  
Pregnant Women ◽  
Viral Entry ◽  
Cell Entry ◽  
Hiv Positive ◽  
Mrna Levels ◽  
Black Race ◽  
Entry Receptor ◽  
Lower Expression ◽  
Human Placentae

Abstract Background SARS-CoV-2 binding receptor ACE2 and the spike protein priming protease TMPRSS2 are co-expressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART). Methods We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2 and L-SIGN (an alternative entry receptor) by qPCR in 105 placentae: 45 from pregnant women with HIV (WHIV) exposed to protease inhibitor (PI)-based ART, 17 from WHIV on non-PI-based ART, and 43 from HIV-uninfected women. Results ACE2 levels were lower, while L-SIGN levels were higher in placentae from WHIV on PI-based ART as compared to those on non-PI-based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses. Discussion We have identified pregnant women of Black race and WHIV who are on PI-based ART to have relatively lower expression of placental ACE2 than those of White race and HIV-uninfected women. This effect may potentially contribute to altered susceptibility to COVID-19 in these women, either favorably; by reduced viral entry, or detrimentally; by loss of ACE2 protection against hyperinflammation.

scholarly journals Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor

2016 ◽  
Vol 90 (7) ◽  
pp. 3366-3384 ◽  
Author(s):  
Sanjay Sarkar ◽  
Lakshman Chelvarajan ◽  
Yun Young Go ◽  
Frank Cook ◽  
Sergey Artiushin ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Critical Role ◽  
Equine Arteritis Virus ◽  
Cell Entry ◽  
Significant Advance ◽  
Type I ◽  
Small Interfering Rnas ◽  
Chromosome 11 ◽  
Trade Restrictions ◽  
Entry Receptor

ABSTRACTPrevious studies in our laboratory have identified equine CXCL16 (EqCXCL16) to be a candidate molecule and possible cell entry receptor for equine arteritis virus (EAV). In horses, the CXCL16 gene is located on equine chromosome 11 (ECA11) and encodes a glycosylated, type I transmembrane protein with 247 amino acids. Stable transfection of HEK-293T cells with plasmid DNA carrying EqCXCL16 (HEK-EqCXCL16 cells) increased the proportion of the cell population permissive to EAV infection from <3% to almost 100%. The increase in permissiveness was blocked either by transfection of HEK-EqCXCL16 cells with small interfering RNAs (siRNAs) directed against EqCXCL16 or by pretreatment with guinea pig polyclonal antibody against EqCXCL16 protein (Gp anti-EqCXCL16 pAb). Furthermore, using a virus overlay protein-binding assay (VOPBA) in combination with far-Western blotting, gradient-purified EAV particles were shown to bind directly to the EqCXCL16 proteinin vitro. The binding of biotinylated virulent EAV strain Bucyrus at 4°C was significantly higher in HEK-EqCXCL16 cells than nontransfected HEK-293T cells. Finally, the results demonstrated that EAV preferentially infects subpopulations of horse CD14+monocytes expressing EqCXCL16 and that infection of these cells is significantly reduced by pretreatment with Gp anti-EqCXCL16 pAb. The collective data from this study provide confirmatory evidence that the transmembrane form of EqCXCL16 likely plays a major role in EAV host cell entry processes, possibly acting as a primary receptor molecule for this virus.IMPORTANCEOutbreaks of EVA can be a source of significant economic loss for the equine industry from high rates of abortion in pregnant mares, death in young foals, establishment of the carrier state in stallions, and trade restrictions imposed by various countries. Similar to other arteriviruses, EAV primarily targets cells of the monocyte/macrophage lineage, which, when infected, are believed to play a critical role in EVA pathogenesis. To this point, however, the host-specified molecules involved in EAV binding and entry into monocytes/macrophages have not been identified. Identification of the cellular receptors for EAV may provide insights to design antivirals and better prophylactic reagents. In this study, we have demonstrated that EqCXCL16 acts as an EAV entry receptor in EAV-susceptible cells, equine monocytes. These findings represent a significant advance in our understanding of the fundamental mechanisms associated with the entry of EAV into susceptible cells.

scholarly journals Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network

2020 ◽  
Author(s):  
Wei Li ◽  
Shuai Yang ◽  
Peng Xu ◽  
Dapeng Zhang ◽  
Ying Tong ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Underlying Mechanism ◽  
Cell Entry ◽  
Clinical Progression ◽  
Health Crisis ◽  
Effective Strategies ◽  
Public Health Crisis ◽  
Human Genomic ◽  
Hyaluronan Synthase 2 ◽  
Entry Receptor

SUMMARYThe COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as “human identical sequences (HIS)”. HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.

TMPRSS2-Inhibitors Play a role in Cell Entry Mechanism of COVID-19: An Insight into Camostat and Nafamostat

2020 ◽  
Author(s):  
Anne Weissenstein
Keyword(s):  
Respiratory Tract ◽  
Cell Entry ◽  
Spike Protein ◽  
Cell Surfaces ◽  
Human Respiratory Tract ◽  
Proteolytic Activation ◽  
Insight Into ◽  
Entry Mechanism

The enzymes trypsin, furin and other proprotein-convertasen, cathepsin, transmembrane proteases (TMPRSS) and elastases play a role by the cell entry of Coronaviren (Coronaviridae). The proteases TMPRSS2 and TMPRSS11a, which exist in the respiratory tract richly and become experiment on cell surfaces, promote the entry of SARS-CoV-1-virus. For the TMPRSS-protease TMPRSS11d - also as protease similar to trypsin has confessed of the human respiratory tract - a proteolytic activation of the spike protein was proved by SARS-CoV.

scholarly journals Mycoplasma testudineum sp. nov., from a desert tortoise (Gopherus agassizii) with upper respiratory tract disease

2004 ◽  
Vol 54 (5) ◽  
pp. 1527-1529 ◽  
Author(s):  
D. R. Brown ◽  
J. L. Merritt ◽  
E. R. Jacobson ◽  
P. A. Klein ◽  
J. G. Tully ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Rrna Gene ◽  
Gopherus Agassizii ◽  
Upper Respiratory Tract ◽  
Respiratory Tract Disease ◽  
Sequence Comparisons ◽  
A Cell ◽  
Upper Respiratory ◽  
Tract Disease ◽  
Mohave Desert

Mycoplasma testudineum sp. nov., first cultured from the upper respiratory tract of a clinically ill tortoise (Gopherus agassizii) in the Mohave Desert, was distinguished from previously described mollicutes serologically and by 16S rRNA gene sequence comparisons. It lacks a cell wall; ferments glucose, mannose, lactose and sucrose; does not produce ‘film and spots’; does not hydrolyse arginine, aesculin or urea; is sensitive to digitonin; and lacks phosphatase activity. The organism causes chronic rhinitis and conjunctivitis of tortoises. The type strain of M. testudineum is BH29T (=ATCC 700618T=MCCM 03231T).

scholarly journals Nonhuman Transferrin Receptor 1 Is an Efficient Cell Entry Receptor for Ocozocoautla de Espinosa Virus

2013 ◽  
Vol 87 (24) ◽  
pp. 13930-13935 ◽  
Author(s):  
Y. Cai ◽  
S. Yu ◽  
S. Mazur ◽  
L. Dong ◽  
K. Janosko ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Cell Entry ◽  
Transferrin Receptor 1 ◽  
Entry Receptor

scholarly journals Activation of a Cell Entry Pathway Common to Type C Mammalian Retroviruses by Soluble Envelope Fragments

2000 ◽  
Vol 74 (1) ◽  
pp. 295-304 ◽  
Author(s):  
Dimitri Lavillette ◽  
Alessia Ruggieri ◽  
Stephen J. Russell ◽  
François-Loïc Cosset
Keyword(s):  
Specific Interaction ◽  
Cell Entry ◽  
Target Cells ◽  
Amino Terminal ◽  
Entry Pathway ◽  
Defective Mutant ◽  
Fusion Defect ◽  
A Cell ◽  
Type C ◽  
Leukemia Viruses

ABSTRACT Mutations that negatively or positively affect the fusion properties of murine leukemia viruses (MLVs) have been found within all subdomains of their SU (surface) and TM (transmembrane) envelope units. Yet, the interrelations between these different regions of the envelope complex during the cell entry process are still elusive. Deletion of the histidine residue of the conserved PHQV motif at the amino terminus of the amphotropic or the ecotropic MLV SU resulted in the AdelH or the MOdelH fusion-defective mutant envelope, respectively. These delH mutant envelopes are incorporated on retroviral particles at normal densities and normally mediate virion binding to cells expressing the retroviral receptors. However, both their cell-cell and virus-cell fusogenicities were fully prevented at an early postbinding stage. We show here that the fusion defect of AdelH or MOdelH envelopes was also almost completely reverted by providing either soluble SU or a polypeptide encompassing the receptor-binding domain (RBD) to the target cells, provided that the integrity of the amino-terminal end of either polypeptide was preserved. Restoration of delH envelope fusogenicity was caused by activation of the target cells via specific interaction of the latter polypeptides with the retrovirus receptor rather than by their association with the delH envelope complexes. Moreover crossactivation of the target cells, leading to fusion activation of AdelH or MOdelH envelopes, was achieved by polypeptides containing various type C mammalian retrovirus RBDs, irrespective of the type of entry-defective glycoprotein that was used for infection. Our results indicate that although they recognize different receptors for binding to the cell surface, type C mammalian retroviruses use a common entry pathway which is activated by a conserved feature of their envelope glycoproteins.

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