scholarly journals A Single Amino Acid Change in the Murine Leukemia Virus Capsid Gene Responsible for theFv1nr Phenotype

2000 ◽  
Vol 74 (11) ◽  
pp. 5385-5387 ◽  
Author(s):  
Yong Tae Jung ◽  
Christine A. Kozak
Keyword(s):  
Amino Acid ◽  
Murine Leukemia Virus ◽  
Amino Acid Change ◽  
Leukemia Virus ◽  
Single Amino Acid ◽  
Amino Acid Difference ◽  
Site Specific ◽  
Single Amino Acid Change ◽  
Leukemia Viruses ◽  
Murine Leukemia

ABSTRACT The nr allele at the mouse Fv1 restriction locus governs resistance to B-tropic and some N-tropic murine leukemia viruses (MLVs). Sequence analysis and site-specific mutagenesis of N-tropic MLVs identified a single amino acid difference responsible for this restriction that is distinct from the site that governs N or B tropism. Viruses with other substitutions at this site were evaluated for altered replication patterns.

scholarly journals Antagonism of BST-2/Tetherin Is a Conserved Function of the Env Glycoprotein of Primary HIV-2 Isolates

2016 ◽  
Vol 90 (24) ◽  
pp. 11062-11074 ◽  
Author(s):  
Chia-Yen Chen ◽  
Masashi Shingai ◽  
Sarah Welbourn ◽  
Malcolm A. Martin ◽  
Pedro Borrego ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Change ◽  
Mixed Population ◽  
Single Amino Acid ◽  
Amino Acid Difference ◽  
Virus Release ◽  
Host Restriction ◽  
Single Amino Acid Change ◽  
Hiv 1 ◽  
Env Glycoprotein

ABSTRACTAlthough HIV-2 does not encode avpugene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino-acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu-like activity to an inactive Env variant. Surprisingly, however, absence of Vpu-like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit.IMPORTANCELentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode avpugene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2 in some isolates. Here, we cloned multiple Env sequences from 7 HIV-2-infected patients and found that about half were able to antagonize BST-2. Importantly, most HIV-2 patients harbored a mixed population of viruses containing or lacking the ability to antagonize BST-2. In fact, in comparing Env sequences from one patient combined with site-directed mutagenesis, we were able to restore BST-2 antagonism to an inactive Env protein by a single-amino-acid change. Our data suggest that targeting BST-2 by HIV-2 Env is a dynamic process that can be regulated by simple changes in the Env sequence.

scholarly journals Identification of the Regions of Fv1 Necessary for Murine Leukemia Virus Restriction

2001 ◽  
Vol 75 (11) ◽  
pp. 5182-5188 ◽  
Author(s):  
Kate N. Bishop ◽  
Michael Bock ◽  
Greg Towers ◽  
Jonathan P. Stoye
Keyword(s):  
Amino Acid ◽  
Virus Replication ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Single Amino Acid ◽  
Viral Capsid ◽  
Amino Acid Substitutions ◽  
Terminal Portion ◽  
Major Homology Region ◽  
Murine Leukemia

ABSTRACT The Fv1 gene restricts murine leukemia virus replication via an interaction with the viral capsid protein. To study this interaction, a number of mutations, including a series of N-terminal and C-terminal deletions, internal deletions, and a number of single-amino-acid substitutions, were introduced into the n and b alleles of the Fv1 gene and the effects of these changes on virus restriction were measured. A significant fraction of the Fv1 protein was not required for restriction; however, retention of an intact major homology region as well as of domains toward the N and C termini was essential. Binding specificity appeared to be a combinatorial property of a number of residues within the C-terminal portion of Fv1.

scholarly journals Generation of Novel Syncytium-Inducing and Host Range Variants of Ecotropic Moloney Murine Leukemia Virus in Mus spicilegus

2003 ◽  
Vol 77 (9) ◽  
pp. 5065-5072 ◽  
Author(s):  
Yong Tae Jung ◽  
Christine A. Kozak
Keyword(s):  
Amino Acid ◽  
Host Range ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Wild Mouse ◽  
Cell Surface Receptor ◽  
Single Amino Acid ◽  
Mus Spicilegus ◽  
Ecotropic Virus ◽  
Murine Leukemia

ABSTRACT Mus spicilegus is an Eastern European wild mouse species that has previously been reported to harbor an unusual infectious ecotropic murine leukemia virus (MLV) and proviral envelope genes of a novel MLV subgroup. In the present study, M. spicilegus neonates were inoculated with Moloney ecotropic MLV (MoMLV). All 17 inoculated mice produced infectious ecotropic virus after 8 to 14 weeks, and two unusual phenotypes distinguished the isolates from MoMLV. First, most of the M. spicilegus isolates grew to equal titers on M. dunni and SC-1 cells, although MoMLV does not efficiently infect M. dunni cells. The deduced amino acid sequence of a representative clone differed from MoMLV by insertion of two serine residues within the VRA of SUenv. Modification of a molecular clone of MoMLV by the addition of these serines produced a virus that grows to high titer in M. dunni cells, establishing a role for these two serine residues in host range. A second unusual phenotype was found in only one of the M. spicilegus isolates, Spl574. Spl574 produces large syncytia of multinucleated giant cells in M. dunni cells, but its replication is restricted in other mouse cell lines. Sequencing and mutagenesis demonstrated that syncytium formation could be attributed to a single amino acid substitution within VRA, S82F. Thus, viruses with altered growth properties are selected during growth in M. spicilegus. The mutations associated with the host range and syncytium-inducing variants map to a key region of VRA known to govern interactions with the cell surface receptor, suggesting that the associated phenotypes may result from altered interactions with the unusual ecotropic virus mCAT1 receptor carried by M. dunni.

scholarly journals Antigenic Subclasses of Polytropic Murine Leukemia Virus (MLV) Isolates Reflect Three Distinct Groups of Endogenous Polytropic MLV-Related Sequences in NFS/N Mice

2003 ◽  
Vol 77 (19) ◽  
pp. 10327-10338 ◽  
Author(s):  
Leonard H. Evans ◽  
Marc Lavignon ◽  
Marc Taylor ◽  
A. S. M. Alamgir
Keyword(s):  
Phylogenetic Analyses ◽  
Leukemia Virus ◽  
Structural Features ◽  
Major Determinant ◽  
Single Amino Acid ◽  
Amino Acid Difference ◽  
Recombinant Viruses ◽  
Different Populations ◽  
Leukemia Viruses ◽  
Murine Leukemia

ABSTRACT Polytropic murine leukemia viruses (MLVs) are generated by recombination of ecotropic MLVs with members of a family of endogenous proviruses in mice. Previous studies have indicated that polytropic MLV isolates comprise two mutually exclusive antigenic subclasses, each of which is reactive with one of two monoclonal antibodies termed MAb 516 and Hy 7. A major determinant of the epitopes distinguishing the subclasses mapped to a single amino acid difference in the SU protein. Furthermore, distinctly different populations of the polytropic MLV subclasses are generated upon inoculation of different ecotropic MLVs. Here we have characterized the majority of endogenous polytropic MLV-related proviruses of NFS/N mice. Most of the proviruses contain intact sequences encoding the receptor-binding region of the SU protein and could be distinguished by sequence heterogeneity within that region. We found that the endogenous proviruses comprise two major groups that encode the major determinant for Hy 7 or MAb 516 reactivity. The Hy 7-reactive proviruses correspond to previously identified polytropic proviruses, while the 516-reactive proviruses comprise the modified polytropic proviruses as well as a third group of polytropic MLV-related proviruses that exhibit distinct structural features. Phylogenetic analyses indicate that the latter proviruses reflect features of phylogenetic intermediates linking xenotropic MLVs to the polytropic and modified polytropic proviruses. These studies elucidate the relationships of the antigenic subclasses of polytropic MLVs to their endogenous counterparts, identify a new group of endogenous proviruses, and identify distinguishing characteristics of the proviruses that should facilitate a more precise description of their expression in mice and their participation in recombination to generate recombinant viruses.

scholarly journals Envelope Proteins Containing Single Amino Acid Substitutions Support a Structural Model of the Receptor-Binding Domain of Bovine Leukemia Virus Surface Protein

2002 ◽  
Vol 76 (21) ◽  
pp. 10861-10872 ◽  
Author(s):  
Elizabeth R. Johnston ◽  
Lorraine M. Albritton ◽  
Kathryn Radke
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Bovine Leukemia Virus ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Binding Domain ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Env Protein ◽  
Murine Leukemia

ABSTRACT Functional domains of the strikingly conserved envelope (Env) glycoproteins of bovine leukemia virus (BLV) and its close relative, human T-cell leukemia virus type 1 (HTLV-1), are still being defined. We have used BLV Env protein variants to gain insights into the structure and function of this important determinant of viral infectivity. Each of 23 different single amino acid variants found in cDNA clones of env transcripts present after short-term culture of peripheral blood mononuclear cells from BLV-infected sheep was expressed in COS-1 cells and tested for the ability to mediate cell fusion and to be cleaved to surface (SU) and transmembrane (TM) protein subunits. Of 11 Env variants that failed to induce syncytia or did so poorly, 7 contained changes in amino acids identical or chemically conserved in the HTLV-1 Env protein. These seven included the four variants that showed aberrant proteolytic cleavage and poor cell surface expression, underscoring their importance for Env structure. Ten of 12 variants that retained wild-type syncytium-inducing ability clustered in the N-terminal half of BLV SU, which forms the putative receptor-binding domain (RBD). Several variants in the RBD showed evidence of subtle misfolding, as judged by reduced binding to monoclonal antibodies recognizing conformational epitopes F, G, and H formed by the N terminus of SU. We modeled the BLV RBD by aligning putative structural elements with known elements of the ecotropic Friend murine leukemia virus RBD monomer. All the variant RBD residues but one are exposed on the surface of this BLV model. These variants as well as function-altering, antibody-reactive residues defined by other investigators group on one face of the molecular model. They are strikingly absent from the opposite face, implying that it is likely to face inward in Env complexes. This surface might interact with the C-terminal domain of SU or with an adjacent monomer in the Env oligomer. This location suggests an orientation for the monomer of ecotropic Friend murine leukemia virus RBD.

scholarly journals Single Amino Acid Insertion in Loop 4 Confers Amphotropic Murine Leukemia Virus Receptor Function upon Murine Pit1

1998 ◽  
Vol 72 (5) ◽  
pp. 4524-4527 ◽  
Author(s):  
Mikkel D. Lundorf ◽  
Finn S. Pedersen ◽  
Bryan O’Hara ◽  
Lene Pedersen
Keyword(s):  
Amino Acid ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Single Amino Acid ◽  
Receptor Function ◽  
Amphotropic Murine Leukemia Virus ◽  
Gibbon Ape Leukemia Virus ◽  
Murine Leukemia

ABSTRACT Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch of amino acids named region A was identified in Pit1 (residues 550 to 558 in loop 4) as critical for GALV and FeLV-B receptor function. We have here investigated the role of region A in A-MuLV and 10A1 entry. Insertion of a single amino acid in region A of mouse Pit1 resulted in a functional A-MuLV receptor, showing that region A plays a role in A-MuLV infection. Moreover, the downregulation of 10A1 receptor function by changes in region A of human Pit1 indicates that this region is also involved in 10A1 entry. Therefore, region A seems to play a role in infection by all viruses utilizing Pit1 and/or Pit2 as receptors.

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