scholarly journals Avian Sarcoma and Leukosis Virus Envelope Glycoproteins Evolve to Broaden Receptor Usage Under Pressure from Entry Competitors †

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 519 ◽  
Author(s):  
Audelia Munguia ◽  
Mark J. Federspiel
Keyword(s):  
Binding Affinity ◽  
Genetic Selection ◽  
Hypervariable Region ◽  
Surface Proteins ◽  
Soluble Form ◽  
Envelope Glycoproteins ◽  
Virus Envelope ◽  
Receptor Usage ◽  
Hypervariable Regions ◽  
Avian Sarcoma

The subgroup A through E avian sarcoma and leukosis viruses (ASLV(A) through ASLV(E)) are a group of highly related alpharetroviruses that have evolved their envelope glycoproteins to use different receptors to enable efficient virus entry due to host resistance and/or to expand host range. Previously, we demonstrated that ASLV(A) in the presence of a competitor to the subgroup A Tva receptor, SUA-rIgG immunoadhesin, evolved to use other receptor options. The selected mutant virus, RCASBP(A)Δ155–160, modestly expanded its use of the Tvb and Tvc receptors and possibly other cell surface proteins while maintaining the binding affinity to Tva. In this study, we further evolved the Δ155–160 virus with the genetic selection pressure of a soluble form of the Tva receptor that should force the loss of Tva binding affinity in the presence of the Δ155–160 mutation. Viable ASLVs were selected that acquired additional mutations in the Δ155–160 Env hypervariable regions that significantly broadened receptor usage to include Tvb and Tvc as well as retaining the use of Tva as a receptor determined by receptor interference assays. A similar deletion in the hr1 hypervariable region of the subgroup C ASLV glycoproteins evolved to broaden receptor usage when selected on Tvc-negative cells.

scholarly journals Model of the TVA Receptor Determinants Required for Efficient Infection by Subgroup A Avian Sarcoma and Leukosis Viruses

2014 ◽  
Vol 89 (4) ◽  
pp. 2136-2148 ◽  
Author(s):  
Deborah C. Melder ◽  
Gennett M. Pike ◽  
Matthew W. VanBrocklin ◽  
Mark J. Federspiel
Keyword(s):  
Binding Affinity ◽  
Conformational Changes ◽  
Critical Level ◽  
Surface Glycoprotein ◽  
Envelope Glycoproteins ◽  
Wild Type ◽  
Targeted Gene Delivery ◽  
Retrovirus Infection ◽  
Avian Sarcoma

ABSTRACTThe study of the interactions of subgroup A avian sarcoma and leucosis viruses [ASLV(A)] with the TVA receptor required to infect cells offers a powerful experimental model of retroviral entry. Several regions and specific residues in the TVA receptor have previously been identified to be critical determinants of the binding affinity with ASLV(A) envelope glycoproteins and to mediate efficient infection. Two homologs of the TVA receptor have been cloned: the original quail TVA receptor, which has been the basis for most of the initial characterization of the ASLV(A) TVA, and the chicken TVA receptor, which is 65% identical to the quail receptor overall but identical in the region thought to be critical for infection. Our previous work characterized three mutant ASLV(A) isolates that could efficiently bind and infect cells using the chicken TVA receptor homolog but not using the quail TVA receptor homolog, with the infectivity of one mutant virus being >500-fold less with the quail TVA receptor. The mutant viruses contained mutations in the hr1 region of the surface glycoprotein. Using chimeras of the quail and chicken TVA receptors, we have identified new residues of TVA critical for the binding affinity and entry of ASLV(A) using the mutant glycoproteins and viruses to probe the function of those residues. The quail TVA receptor required changes at residues 10, 14, and 31 of the corresponding chicken TVA residues to bind wild-type and mutant ASLV(A) glycoproteins with a high affinity and recover the ability to mediate efficient infection of cells. A model of the TVA determinants critical for interacting with ASLV(A) glycoproteins is proposed.IMPORTANCEA detailed understanding of how retroviruses enter cells, evolve to use new receptors, and maintain efficient entry is crucial for identifying new targets for combating retrovirus infection and pathogenesis, as well as for developing new approaches for targeted gene delivery. Since all retroviruses share an envelope glycoprotein organization, they likely share a mechanism of receptor triggering to begin the entry process. Multiple, noncontiguous interaction determinants located in the receptor and the surface (SU) glycoprotein hypervariable domains are required for binding affinity and to restrict or broaden receptor usage. In this study, further mechanistic details of the entry process were elucidated by characterizing the ASLV(A) glycoprotein interactions with the TVA receptor required for entry. The ASLV(A) envelope glycoproteins are organized into functional domains that allow changes in receptor choice to occur by mutation and/or recombination while maintaining a critical level of receptor binding affinity and an ability to trigger glycoprotein conformational changes.

scholarly journals Reverse Engineering Provides Insights on the Evolution of Subgroups A to E Avian Sarcoma and Leukosis Virus Receptor Specificity

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 497 ◽  
Author(s):  
Mark J. Federspiel
Keyword(s):  
Reverse Engineering ◽  
Conformational Changes ◽  
Envelope Glycoprotein ◽  
Genetic Selection ◽  
Experimental System ◽  
Initial Step ◽  
Cellular Protein ◽  
Viral Fusion ◽  
Virus Envelope ◽  
Avian Sarcoma

The initial step of retrovirus entry—the interaction between the virus envelope glycoprotein trimer and a cellular receptor—is complex, involving multiple, noncontiguous determinants in both proteins that specify receptor choice, binding affinity and the ability to trigger conformational changes in the viral glycoproteins. Despite the complexity of this interaction, retroviruses have the ability to evolve the structure of their envelope glycoproteins to use a different cellular protein as receptors. The highly homologous subgroup A to E Avian Sarcoma and Leukosis Virus (ASLV) glycoproteins belong to the group of class 1 viral fusion proteins with a two-step triggering mechanism that allows experimental access to intermediate structures during the fusion process. We and others have taken advantage of replication-competent ASLVs and exploited genetic selection strategies to force the ASLVs to naturally evolve and acquire envelope glycoprotein mutations to escape the pressure on virus entry and still yield a functional replicating virus. This approach allows for the simultaneous selection of multiple mutations in multiple functional domains of the envelope glycoprotein that may be required to yield a functional virus. Here, we review the ASLV family and experimental system and the reverse engineering approaches used to understand the evolution of ASLV receptor usage.

scholarly journals Mutations in Both the Surface and Transmembrane Envelope Glycoproteins of the RAV-2 Subgroup B Avian Sarcoma and Leukosis Virus Are Required to Escape the Antiviral Effect of a Secreted Form of the TvbS3 Receptor †

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 500 ◽  
Author(s):  
Xueqian Yin ◽  
Deborah C. Melder ◽  
William S. Payne ◽  
Jerry B. Dodgson ◽  
Mark J. Federspiel
Keyword(s):  
Virus Entry ◽  
Genetic Selection ◽  
Antiviral Effect ◽  
Viral Envelope ◽  
Host Protein ◽  
Surface Glycoprotein ◽  
Selection Strategies ◽  
Hypervariable Regions ◽  
Multiple Regions ◽  
Avian Sarcoma

The subgroup A through E avian sarcoma and leukosis viruses ASLV(A) through ASLV(E) are a group of highly related alpharetroviruses that have evolved to use very different host protein families as receptors. We have exploited genetic selection strategies to force the replication-competent ASLVs to naturally evolve and acquire mutations to escape the pressure on virus entry and yield a functional replicating virus. In this study, evolutionary pressure was exerted on ASLV(B) virus entry and replication using a secreted for of its Tvb receptor. As expected, mutations in the ASLV(B) surface glycoprotein hypervariable regions were selected that knocked out the ability for the mutant glycoprotein to bind the sTvbS3-IgG inhibitor. However, the subgroup B Rous associated virus 2 (RAV-2) also required additional mutations in the C-terminal end of the SU glycoprotein and multiple regions of TM highlighting the importance of the entire viral envelope glycoprotein trimer structure to mediate the entry process efficiently. These mutations altered the normal two-step ASLV membrane fusion process to enable infection.

scholarly journals Identification of Key Residues in Subgroup A Avian Leukosis Virus Envelope Determining Receptor Binding Affinity and Infectivity of Cells Expressing Chicken or Quail Tva Receptor

2001 ◽  
Vol 75 (2) ◽  
pp. 726-737 ◽  
Author(s):  
Sheri L. Holmen ◽  
Deborah C. Melder ◽  
Mark J. Federspiel
Keyword(s):  
Binding Affinity ◽  
Receptor Binding ◽  
Retroviral Vectors ◽  
Avian Leukosis Virus ◽  
Surface Glycoprotein ◽  
Envelope Glycoproteins ◽  
Virus Propagation ◽  
Virus Envelope ◽  
Receptor Binding Affinity ◽  
Extracellular Region

ABSTRACT To better understand retroviral entry, we have characterized the interactions between subgroup A avian leukosis virus [ALV(A)] envelope glycoproteins and Tva, the receptor for ALV(A), that result in receptor interference. We have recently shown that soluble forms of the chicken and quail Tva receptor (sTva), expressed from genes delivered by retroviral vectors, block ALV(A) infection of cultured chicken cells (∼200-fold antiviral effect) and chickens (>98% of the birds were not infected). We hypothesized that inhibition of viral replication by sTva would select virus variants with mutations in the surface glycoprotein (SU) that altered the binding affinity of the subgroup A SU for the sTva protein and/or altered the normal receptor usage of the virus. Virus propagation in the presence of quail sTva-mIgG, the quail Tva extracellular region fused to the constant region of the mouse immunoglobulin G (IgG) protein, identified viruses with three mutations in the subgroup A hr1 region of SU, E149K, Y142N, and Y142N/E149K. These mutations reduced the binding affinity of the subgroup A envelope glycoproteins for quail sTva-mIgG (32-, 324-, and 4,739-fold, respectively) but did not alter their binding affinity for chicken sTva-mIgG. The ALV(A) mutants efficiently infected cells expressing the chicken Tva receptor but were 2-fold (E149K), 10-fold (Y142N), and 600-fold (Y142N/E149K) less efficient at infecting cells expressing the quail Tva receptor. These mutations identify key determinants of the interaction between the ALV(A) glycoproteins and the Tva receptor. We also conclude from these results that, at least for the wild-type and variant ALV(A)s tested, the receptor binding affinity was directly related to infection efficiency.

scholarly journals Characterization of the Oligosaccharides of Inkoo Virus Envelope Glycoproteins

1982 ◽  
Vol 63 (2) ◽  
pp. 425-434 ◽  
Author(s):  
M. Pesonen ◽  
R. Ronnholm ◽  
E. Kuismanen ◽  
R. F. Pettersson
Keyword(s):  
Envelope Glycoproteins ◽  
Virus Envelope

scholarly journals Stable expression and potential use of West Nile virus envelope glycoproteins preM/E as antigen in diagnostic tests

2011 ◽  
Vol 42 (3) ◽  
pp. 1161-1166 ◽  
Author(s):  
Juliana Felipetto Cargnelutti ◽  
Mário Celso Sperotto Brum ◽  
Rudi Weiblen ◽  
Eduardo Furtado Flores
Keyword(s):  
West Nile Virus ◽  
Diagnostic Tests ◽  
Stable Expression ◽  
Envelope Glycoproteins ◽  
Virus Envelope ◽  
West Nile ◽  
Potential Use

330 MOLECULAR SIGNATURES OF HEPATITIS C VIRUS ENVELOPE GLYCOPROTEINS AND RESPONSE TO ANTIVIRAL TREATMENT

2009 ◽  
Vol 50 ◽  
pp. S128
Author(s):  
R. Moenne-Loccoz ◽  
C. Rajafinjatovo ◽  
S. Fafi-Kremer ◽  
F. Habersetzer ◽  
A. Ananna ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Treatment ◽  
Envelope Glycoproteins ◽  
Molecular Signatures ◽  
Virus Envelope

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.

Sign in / Sign up

Export Citation Format

Share Document