scholarly journals Elucidating the antiviral mechanism of different MARCH factors

2020 ◽  
Author(s):  
Supawadee Umthong ◽  
Brian Lynch ◽  
Uddhav Timilsina ◽  
Brandon Waxman ◽  
Emily B. Ivey ◽  
...  
Keyword(s):  
Transmembrane Proteins ◽  
Comprehensive Analysis ◽  
Envelope Glycoproteins ◽  
Main Function ◽  
Intrinsic Immunity ◽  
Immunodeficiency Virus ◽  
Antiviral Function ◽  
Antiviral Mechanism ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

ABSTRACTThe Membrane Associated RING-CH (MARCH) proteins belong to a family of E3 ubiquitin ligases, whose main function is to remove transmembrane proteins from the plasma membrane. Recent work has shown that the human MARCH1, 2 and 8 are antiretroviral factors that target the Human Immunodeficiency virus-1 (HIV-1) envelope glycoproteins by reducing their incorporation in the budding virions. Nevertheless, the dearth of information regarding the antiviral mechanism of this family of proteins necessitates further examination. In this study, using both the human MARCH proteins and their mouse homologues, we provide a comprehensive analysis of the antiretroviral mechanism of this family of proteins. Moreover, we show that human MARCH proteins restrict to varying degrees the envelope glycoproteins of a diverse number of viruses. This report sheds light on the important antiviral function of MARCH proteins and their significance in cell intrinsic immunity.

scholarly journals Elucidating the Antiviral Mechanism of Different MARCH Factors

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Supawadee Umthong ◽  
Brian Lynch ◽  
Uddhav Timilsina ◽  
Brandon Waxman ◽  
Emily B. Ivey ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Comprehensive Analysis ◽  
Envelope Glycoproteins ◽  
Main Function ◽  
Intrinsic Immunity ◽  
Immunodeficiency Virus ◽  
Antiviral Function ◽  
Retrovirus Infection ◽  
Antiviral Mechanism ◽  
Hiv 1

ABSTRACT The membrane-associated RING-CH (MARCH) proteins belong to a family of E3 ubiquitin ligases, whose main function is to remove transmembrane proteins from the plasma membrane. Recent work has shown that the human MARCH1, 2, and 8 are antiretroviral factors that target the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins by reducing their incorporation in the budding virions. Nevertheless, the dearth of information regarding the antiviral mechanism of this family of proteins necessitates further examination. In this study, using both the human MARCH proteins and their mouse homologues, we provide a comprehensive analysis of the antiretroviral mechanism of this family of proteins. Moreover, we show that human MARCH proteins restrict to various degrees the envelope glycoproteins of a diverse number of viruses. This report sheds light on the important antiviral function of MARCH proteins and their significance in cell intrinsic immunity. IMPORTANCE This study examines the mechanism utilized by different MARCH proteins to restrict retrovirus infection. MARCH proteins block the incorporation of envelope glycoproteins to the budding virions. In this report, by comparing the human and mouse MARCH genes and using murine leukemia virus (MLV) and HIV-1, we identify differences in the mechanism of restriction among MARCH proteins. Furthermore, we perform a comprehensive analysis on a number of envelope glycoproteins and show that MARCH proteins have broad antiviral functions.

scholarly journals SERINC5 as a New Restriction Factor for Human Immunodeficiency Virus and Murine Leukemia Virus

2018 ◽  
Vol 5 (1) ◽  
pp. 323-340 ◽  
Author(s):  
Claudia Firrito ◽  
Cinzia Bertelli ◽  
Teresa Vanzo ◽  
Ajit Chande ◽  
Massimo Pizzato
Keyword(s):  
Human Immunodeficiency Virus ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Transmembrane Proteins ◽  
Target Cells ◽  
Restriction Factors ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1 ◽  
Murine Leukemia

SERINC genes encode for homologous multipass transmembrane proteins with unknown cellular function, despite being highly conserved across eukaryotes. Among the five SERINC genes found in humans, SERINC5 was shown to act as a powerful inhibitor of retroviruses. It is efficiently incorporated into virions and blocks the penetration of the viral core into target cells, by impairing the fusion process with a yet unclear mechanism. SERINC5 was also found to promote human immunodeficiency virus 1 (HIV-1) virion neutralization by antibodies, indicating a pleiotropic activity, which remains mostly unexplored. Counteracting factors have emerged independently in at least three retrovirus lineages, underscoring their fundamental importance during retrovirus evolution. Nef and S2 of primate and equine lentiviruses, and glycoGag of gammaretroviruses, act similarly by targeting SERINC5 to endosomes and excluding it from virions. Here, we discuss the features that distinguish SERINC5 from other known restriction factors, delineating a yet unique class of antiviral inhibitors.

scholarly journals Antiviral Activity of a Zymolytic Grain Based Extract on Human Immunodeficiency Virus Type 1In Vitro

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Chu Wang ◽  
Di Liu ◽  
Xiao-Han Guo ◽  
Bin Yu ◽  
Hui Wu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Hiv Treatment ◽  
Cell Binding ◽  
Cytotoxic Effects ◽  
Immunodeficiency Virus ◽  
Antiviral Function ◽  
Antiviral Mechanism ◽  
Viral Surface ◽  
Hiv 1

Increasing evidence shows that grains may play a role in disease prevention beyond the simple provision of energy and nutrients. It has been reported that some components contained in grains exert their functional effects on viral and bacterial infections and protect against various cancers. However, until now, hardly any intervention studies have investigated the effects of grains or grain based extracts on the inhibition of HIV-1 infection. In this study, the antiviral function of a zymolytic grain based extract (ZGE) was detectedin vitroand in rats, and the antiviral mechanism was investigated. Results showed that ZGE had an inhibition effect on HIV-1 infectionin vitrowith low cytotoxic effects. The study of the mechanism demonstrated that this functional food possibly acted on the viral surface structure protein gp120 which is responsible for cell binding, as well as on the postattachment stage of the virus. The sera of model rats administrated with this food by gavage presented anti-infection abilities against HIV-1in vitroduring a serum concentration associated period of time. These findings provide valuable insights into the application of ZGE on the control of viral load, which may contribute to future anti-HIV treatment with less adverse effects.

scholarly journals APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus–1 infection

2011 ◽  
Vol 72 (3) ◽  
pp. 207-212 ◽  
Author(s):  
P.A. Gourraud ◽  
A. Karaouni ◽  
J.M. Woo ◽  
T. Schmidt ◽  
J.R. Oksenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Sequence ◽  
Sequence Diversity ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

scholarly journals A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer

2010 ◽  
Vol 84 (7) ◽  
pp. 3147-3161 ◽  
Author(s):  
Shi-Hua Xiang ◽  
Andrés Finzi ◽  
Beatriz Pacheco ◽  
Kevin Alexander ◽  
Wen Yuan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Receptor Binding ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Envelope Glycoproteins ◽  
V3 Loop ◽  
Virus Envelope ◽  
Hydrophobic Patch ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding of gp120 to receptors on the target cell alters the gp120-gp41 relationship and activates the membrane-fusing capacity of gp41. Interaction of gp120 with the primary receptor, CD4, results in the exposure of the gp120 third variable (V3) loop, which contributes to binding the CCR5 or CXCR4 chemokine receptors. We show here that insertions in the V3 stem or polar substitutions in a conserved hydrophobic patch near the V3 tip result in decreased gp120-gp41 association (in the unliganded state) and decreased chemokine receptor binding (in the CD4-bound state). Subunit association and syncytium-forming ability of the envelope glycoproteins from primary HIV-1 isolates were disrupted more by V3 changes than those of laboratory-adapted HIV-1 envelope glycoproteins. Changes in the gp120 β2, β19, β20, and β21 strands, which evidence suggests are proximal to the V3 loop in unliganded gp120, also resulted in decreased gp120-gp41 association. Thus, a gp120 element composed of the V3 loop and adjacent beta strands contributes to quaternary interactions that stabilize the unliganded trimer. CD4 binding dismantles this element, altering the gp120-gp41 relationship and rendering the hydrophobic patch in the V3 tip available for chemokine receptor binding.

scholarly journals Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.

1989 ◽  
Vol 170 (5) ◽  
pp. 1681-1695 ◽  
Author(s):  
I Berkower ◽  
G E Smith ◽  
C Giri ◽  
D Murphy
Keyword(s):  
Genetic Diversity ◽  
Human Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Neutralizing Epitope ◽  
Vaccine Strategy ◽  
Disease Pathogenesis ◽  
Immunodeficiency Virus ◽  
High Degree ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque-forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected.

scholarly journals Tat–Human Immunodeficiency Virus-1 Induces Human Monocyte Chemotaxis by Activation of Vascular Endothelial Growth Factor Receptor-1

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1365-1372 ◽  
Author(s):  
Stefania Mitola ◽  
Silvano Sozzani ◽  
Walter Luini ◽  
Luca Primo ◽  
Alessandro Borsatti ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Vascular Endothelial ◽  
Immunodeficiency Virus ◽  
Monocyte Chemotaxis ◽  
Endothelial Growth Factor ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti–VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody antiphosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.

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