Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| an intron with a constitutive transport element is retained in a tap messenger rna. | alternative splicing is a key factor contributing to genetic diversity and evolution. intron retention, one form of alternative splicing, is common in plants but rare in higher eukaryotes, because messenger rnas with retained introns are subject to cellular restriction at the level of cytoplasmic export and expression. often, retention of internal introns restricts the export of these mrnas and makes them the targets for degradation by the cellular nonsense-mediated decay machinery if they conta ... | 2006 | 16971948 |
| the conserved dileucine- and tyrosine-based motifs in mlv and mpmv envelope glycoproteins are both important to regulate a common env intracellular trafficking. | retrovirus particles emerge from the assembly of two structural protein components, gag that is translated as a soluble protein in the cytoplasm of the host cells, and env, a type i transmembrane protein. because both components are translated in different intracellular compartments, elucidating the mechanisms of retrovirus assembly thus requires the study of their intracellular trafficking. | 2006 | 16978406 |
| the betaretrovirus mason-pfizer monkey virus selectively excludes simian apobec3g from virion particles. | the apobec3 protein family can constitute a potent barrier to the successful infection of mammalian species by retroviruses. therefore, any retrovirus that has evolved the ability to replicate in a given animal must have developed mechanisms that allow it to avoid or inhibit the apobec3 proteins expressed in that animal. here, we demonstrate that mason-pfizer monkey virus (mpmv) is resistant to inhibition by the apobec3g protein expressed in its normal host, the rhesus macaque, but highly suscep ... | 2006 | 17035335 |
| interacting partners of m-pmv nucleocapsid-dutpase. | the nucleocapsid-dutpase protein of mason-pfizer monkey virus is a truly bifunctional fusion enzyme. the exact role of this fusion protein in the viral life cycle is unclear. to explore its function, we started to identify interacting protein partners of the enzyme in vitro. three viral proteins, integrase, capsid and nucleocapsid, were found to be capable of physical interaction with nc-dutpase. integrase protein is an important component within the preintegration complex; therefore the present ... | 2006 | 17065090 |
| atomic force microscopy investigation of mason-pfizer monkey virus and human immunodeficiency virus type 1 reassembled particles. | particles of deltaprocanc, a fusion of capsid (ca) and nucleocapsid (nc) protein of mason-pfizer monkey virus (m-pmv), which lacks the amino terminal proline, were reassembled in vitro and visualized by atomic force microscopy (afm). the particles, of 83-84 nm diameter, exhibited ordered domains based on trigonal arrays of prominent rings with center to center distances of 8.7 nm. imperfect closure of the lattice on the spherical surface was affected by formation of discontinuities. the lattice ... | 2007 | 17123565 |
| the role of the s-s bridge in retroviral protease function and virion maturation. | retroviral proteases are translated as a part of gag-related polyproteins, and are released and activated during particle release. mason-pfizer monkey virus (m-pmv) gag polyproteins assemble into immature capsids within the cytoplasm of the host cells; however, their processing occurs only after transport to the plasma membrane and subsequent release. thus, the activity of m-pmv protease is expected to be highly regulated during the replication cycle. it has been proposed that reversible oxidati ... | 2007 | 17140600 |
| murine musd retrotransposon: structure and molecular evolution of an "intracellularized" retrovirus. | we had previously identified active autonomous copies of the musd long terminal repeat-retrotransposon family, which have retained transpositional activity. these elements are closely related to betaretroviruses but lack an envelope (env) gene. here we show that these elements encode strictly intracellular virus-like particles that can unambiguously be identified by electron microscopy. we demonstrate intracellular maturation of the particles, with a significant proportion of densely packed core ... | 2007 | 17151128 |
| tap and dbp5, but not gag, are involved in dr-mediated nuclear export of unspliced rous sarcoma virus rna. | all retroviruses must circumvent cellular restrictions on the export of unspliced rnas from the nucleus. while the unspliced rna export pathways for hiv and mason-pfizer monkey virus are well characterized, that of rous sarcoma virus (rsv) is not. we have previously reported that the rsv direct repeat (dr) elements are involved in the cytoplasmic accumulation of unspliced viral rna. here, using fluorescent in situ hybridization (fish), we demonstrate that unspliced viral rnas bearing a single po ... | 2007 | 17328934 |
| multimerization of the p12 domain is necessary for mason-pfizer monkey virus gag assembly in vitro. | mason-pfizer monkey virus (m-pmv) gag protein contains a domain p12 that is unique to this virus (simian retrovirus-3) and its close relatives. the alpha-helical n-terminal half of p12, which contains a leucine zipper-like region, forms ordered structures in e. coli and the c-terminal half can form sds-resistant oligomers in vitro. together these properties suggest that p12 is a strong protein-protein interaction domain that facilitates gag-gag oligomerization. we have analyzed the oligomerizati ... | 2007 | 17490704 |
| the shuttling sr protein 9g8 plays a role in translation of unspliced mrna containing a constitutive transport element. | the splicing regulatory sr protein, 9g8, has recently been proposed to function in mrna export in conjunction with the export protein, tap/nxf1. tap interacts directly with the mason-pfizer monkey virus constitutive transport element (cte), an element that enables export of unspliced, intron-containing mrna. based on our previous finding that tap can promote polysome association and translation of cte-rna, we investigated the effect of 9g8 on cytoplasmic rna fate. 9g8 was shown to enhance expres ... | 2007 | 17513303 |
| basic residues in the mason-pfizer monkey virus gag matrix domain regulate intracellular trafficking and capsid-membrane interactions. | mason-pfizer monkey virus (m-pmv) capsids that have assembled in the cytoplasm must be transported to and associate with the plasma membrane prior to being enveloped by a lipid bilayer during viral release. structural studies have identified a positive-charge density on the membrane-proximal surface of the matrix (ma) protein component of the gag polyprotein. to investigate if basic amino acids in ma play a role in intracellular transport and capsid-membrane interactions, mutants were constructe ... | 2007 | 17596311 |
| nedd4l overexpression rescues the release and infectivity of human immunodeficiency virus type 1 constructs lacking ptap and ypxl late domains. | the cellular escrt pathway functions in membrane remodeling events that accompany endosomal protein sorting, cytokinesis, and enveloped rna virus budding. in the last case, short sequence motifs (termed late domains) within human immunodeficiency virus type 1 (hiv-1) p6(gag) bind and recruit two escrt pathway proteins, tsg101 and alix, to facilitate virus budding. we now report that overexpression of the hect ubiquitin e3 ligase, nedd4l/nedd4-2, stimulated the release of hiv-1 constructs that la ... | 2008 | 18321968 |
| d-retrovirus morphogenetic switch driven by the targeting signal accessibility to tctex-1 of dynein. | despite extensive data demonstrating that immature retroviral particle assembly can take place either at the plasma membrane or at a distinct location within the cytoplasm, targeting of viral precursor proteins to either assembly site still remains poorly understood. biochemical data presented here suggest that tctex-1, a light chain of the molecular motor dynein, is involved in the intracellular targeting of mason-pfizer monkey virus (m-pmv) polyproteins to the cytoplasmic assembly site. compar ... | 2008 | 18647839 |
| amino acid preferences of retroviral proteases for amino-terminal positions in a type 1 cleavage site. | the specificities of the proteases of 11 retroviruses were studied using a series of oligopeptides with amino acid substitutions in the p1, p3, and p4 positions of a naturally occurring type 1 cleavage site (val-ser-gln-asn-tyr downward arrowpro-ile-val-gln) in human immunodeficiency virus type 1 (hiv-1). previously, the substrate specificity of the p2 site was studied for the same representative set of retroviral proteases, which included at least one member from each of the seven genera of the ... | 2008 | 18701588 |
| the effect of point mutations within the n-terminal domain of mason-pfizer monkey virus capsid protein on virus core assembly and infectivity. | retroviral capsid protein (ca) mediates protein interactions driving the assembly of both immature viral particles and the core of the mature virions. structurally conserved n-terminal domains of several retroviruses refold after proteolytic cleavage into a beta-hairpin, stabilized by a salt bridge between conserved n-terminal pro and asp residues. based on comparison with other retroviral ca, we identified asp50 and asp57 as putative interacting partners for pro1 in mason-pfizer monkey virus (m ... | 2008 | 18755489 |
| identification of postentry restrictions to mason-pfizer monkey virus infection in new world monkey cells. | trim5alpha has been shown to be a major postentry determinant of the host range for gammaretroviruses and lentiviruses and, more recently, spumaviruses. however, the restrictive potential of trim5alpha against other retroviruses has been largely unexplored. we sought to determine whether or not mason-pfizer monkey virus (m-pmv), a prototype betaretrovirus isolated from rhesus macaques, was sensitive to restriction by trim5alpha. cell lines from both old world and new world primate species were s ... | 2008 | 18799582 |
| 1h, 13c, and 15n resonance assignment of the n-terminal domain of mason-pfizer monkey virus capsid protein, ca 1-140. | mason-pfizer monkey virus (m-pmv) belongs to the family of betaretroviruses characterized by the assembly of immature particles within cytoplasm of infected cells in contrast to other retroviruses (e.g. hiv, rsv) that assemble their immature particles at a plasma membrane. simultaneously with or shortly after budding a virus-encoded protease is activated and the gag polyprotein is cleaved into three major structural proteins: matrix (ma), capsid (ca), and nucleocapsid (nc) protein. mature retrov ... | 2008 | 19636921 |
| human ubc9 contributes to production of fully infectious human immunodeficiency virus type 1 virions. | ubc9 was identified as a cellular protein that interacts with the gag protein of mason-pfizer monkey virus. we show here that ubc9 also interacts with the human immunodeficiency virus type 1 (hiv-1) gag protein and that their interaction is important for virus replication. gag was found to colocalize with ubc9 predominantly at perinuclear puncta. while cells in which ubc9 expression was suppressed with rna interference produced normal numbers of virions, these particles were 8- to 10-fold less i ... | 2009 | 19640976 |
| conformational changes of the n-terminal part of mason-pfizer monkey virus p12 protein during multimerization. | the mason-pfizer monkey virus is a prototype betaretrovirus with the defining characteristic that it assembles spherical immature particles from gag-related polyprotein precursors within the cytoplasm of the infected cell. it was shown previously that the n-terminal part of the gag p12 domain (wt-np12) is required for efficient assembly. however, the precise role for p12 in mediating gag-gag interaction is still poorly understood. in this study we employed detailed circular dichroism spectroscop ... | 2009 | 19699504 |
| trafficking through the rev/rre pathway is essential for efficient inhibition of human immunodeficiency virus type 1 by an antisense rna derived from the envelope gene. | a human immunodeficiency virus type 1 (hiv-1)-based vector expressing an antisense rna directed against hiv-1 is currently in clinical trials. this vector has shown a remarkable ability to inhibit hiv-1 replication, in spite of the fact that therapeutic use of unmodified antisense rnas has generally been disappointing. to further analyze the basis for this, we examined the effects of different plasmid-based hiv-1 long-terminal-repeat-driven constructs expressing antisense rna to the same target ... | 2009 | 18971264 |
| defining the dna substrate binding sites on hiv-1 integrase. | a tetramer model for human immunodeficiency virus type 1 (hiv-1) integrase (in) with dna representing long terminal repeat (ltr) termini was previously assembled to predict the in residues that interact with the ltr termini; these predictions were experimentally verified for nine amino acid residues [chen, a., weber, i. t., harrison, r. w. & leis, j. (2006). identification of amino acids in hiv-1 and avian sarcoma virus integrase subsites required for specific recognition of the long terminal re ... | 2009 | 19014951 |
| the impact of altered polyprotein ratios on the assembly and infectivity of mason-pfizer monkey virus. | most retroviruses employ a frameshift mechanism during polyprotein synthesis to balance appropriate ratios of structural proteins and enzymes. to investigate the requirements for individual precursors in retrovirus assembly, we modified the polyprotein repertoire of mason-pfizer monkey virus (m-pmv) by mutating the frameshift sites to imitate the polyprotein organization of rous sarcoma virus (gag-pro and gag-pro-pol) or human immunodeficiency virus (gag and gag-pro-pol). for the "rous-like" vir ... | 2009 | 19062065 |
| role of a heterologous retroviral transport element in the development of genetic complementation assay for mouse mammary tumor virus (mmtv) replication. | the mouse mammary tumor virus (mmtv) is a type b retrovirus that is unique from other retroviruses in having multiple "tissue specific" and "hormone inducible" promoters. this unique feature has lead to the increasing interest in studying the biology of mmtv replication with the ultimate goal of developing mmtv based vectors for potentially targeted human gene therapy. in this report, we describe, for the first time, the establishment of an in vivo genetic complementation assay to study various ... | 2009 | 19157480 |
| mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome. | retroviruses have evolved multiple strategies to direct the synthesis of a complex proteome from a single primary transcript. their mechanisms are modulated by a breadth of virus-host interactions, which are of significant fundamental interest because they ultimately affect the efficiency of virus replication and disease pathogenesis. motifs located within the untranslated region (utr) of the retroviral rna have established roles in transcriptional trans-activation, rna packaging, and genome rev ... | 2009 | 19166625 |
| nonmyristoylated matrix protein from the mason-pfizer monkey virus forms oligomers. | we studied the oligomeric properties of betaretroviral nonmyristoylated matrix protein (ma) and its r55f mutant from the mason-pfizer monkey virus in solution by means of chemical crosslinking and nmr spectroscopy. by analyzing crosslinked products and using concentration-dependent nmr chemical shift mapping, we have proven that the wild-type (wt) ma forms oligomers in solution. conversely, no oligomerization was observed for the r55f mutant. structural comparison of mas explained their differen ... | 2009 | 19481092 |
| nmr structure of the n-terminal domain of capsid protein from the mason-pfizer monkey virus. | the high-resolution structure of the n-terminal domain (ntd) of the retroviral capsid protein (ca) of mason-pfizer monkey virus (m-pmv), a member of the betaretrovirus family, has been determined by nmr. the m-pmv ntd ca structure is similar to the other retroviral capsid structures and is characterized by a six alpha-helix bundle and an n-terminal beta-hairpin, stabilized by an interaction of highly conserved residues, pro1 and asp57. since the role of the beta-hairpin has been shown to be crit ... | 2009 | 19527730 |
| cross-packaging of genetically distinct mouse and primate retroviral rnas. | the mouse mammary tumor virus (mmtv) is unique from other retroviruses in having multiple viral promoters, which can be regulated by hormones in a tissue specific manner. this unique property has lead to increased interest in studying mmtv replication with the hope of developing mmtv based vectors for human gene therapy. however, it has recently been reported that related as well as unrelated retroviruses can cross-package each other's genome raising safety concerns towards the use of candidate ... | 2009 | 19602292 |
| mechanisms controlling titer and expression of bidirectional lentiviral and gammaretroviral vectors. | bidirectional lentiviral vectors mediate expression of two or more cdnas from a single internal promoter. in this study, we examined mechanisms that control titer and expression properties of this vector system. to address whether the bidirectional design depends on lentiviral (lv) backbone components, especially the rev/rev responsive element (rre) system, we constructed similar expression cassettes for lv and gammaretroviral (gv) vectors. bidirectional expression levels could be adjusted by th ... | 2010 | 19847204 |
| effect of dimerizing domains and basic residues on in vitro and in vivo assembly of mason-pfizer monkey virus and human immunodeficiency virus. | assembly of immature retroviral particles is a complex process involving interactions of several specific domains of the gag polyprotein localized mainly within capsid protein (ca), spacer peptide (sp), and nucleocapsid protein (nc). in the present work we focus on the contribution of nc to the oligomerization of ca leading to assembly of mason-pfizer monkey virus (m-pmv) and hiv-1. analyzing in vitro assembly of substitution and deletion mutants of deltaprocanc, we identified a "spacer-like" se ... | 2010 | 20007269 |
| a g-c-rich palindromic structural motif and a stretch of single-stranded purines are required for optimal packaging of mason-pfizer monkey virus (mpmv) genomic rna. | during retroviral rna packaging, two copies of genomic rna are preferentially packaged into the budding virus particles whereas the spliced viral rnas and the cellular rnas are excluded during this process. specificity towards retroviral rna packaging is dependent upon sequences at the 5' end of the viral genome, which at times extend into gag sequences. it has earlier been suggested that the mason-pfizer monkey virus (mpmv) contains packaging sequences within the 5' untranslated region (utr) an ... | 2010 | 20600114 |
| conserved and variable features of gag structure and arrangement in immature retrovirus particles. | the assembly of retroviruses is driven by oligomerization of the gag polyprotein. we have used cryo-electron tomography together with subtomogram averaging to describe the three-dimensional structure of in vitro-assembled gag particles from human immunodeficiency virus, mason-pfizer monkey virus, and rous sarcoma virus. these represent three different retroviral genera: the lentiviruses, betaretroviruses and alpharetroviruses. comparison of the three structures reveals the features of the supram ... | 2010 | 20810738 |
| reciprocal cross-packaging of primate lentiviral (hiv-1 and siv) rnas by heterologous non-lentiviral mpmv proteins. | retroviral rna packaging signal (ψ) allows the preferential packaging of genomic rna into virus particles through its interaction with the nucleocapsid protein. the specificity of this interaction came into question when it was shown that primate retroviruses, such as hiv-1, could cross-package rna from its simian cousin, siv, and vice versa and that feline retrovirus, fiv could cross-package rna from a distantly related primate retrovirus, mpmv. to study the generality of this phenomenon furthe ... | 2010 | 20875467 |
| oligomerization of a retroviral matrix protein is facilitated by backbone flexibility on nanosecond time scale. | the oligomerization capacity of the retroviral matrix protein is an important feature that affects assembly of immature virions and their interaction with cellular membrane. a combination of nmr relaxation measurements and advanced analysis of molecular dynamics simulation trajectory provided an unprecedentedly detailed insight into internal mobility of matrix proteins of the mason-pfizer monkey virus. strong evidence have been obtained that the oligomerization capacity of the wild-type matrix p ... | 2011 | 21366213 |
| expression and purification of myristoylated matrix protein of mason-pfizer monkey virus for nmr and ms measurements. | matrix proteins play multiple roles both in early and late stages of the viral replication cycle. their n-terminal myristoylation is important for interaction with the host cell membrane during virus budding. we used escherichia coli, carrying n-myristoyltransferase gene, for the expression of the myristoylated his-tagged matrix protein of mason-pfizer monkey virus. an efficient, single-step purification procedure eliminating all contaminating proteins including, importantly, the non-myristoylat ... | 2011 | 21640189 |
| clathrin facilitates the morphogenesis of retrovirus particles. | the morphogenesis of retroviral particles is driven by gag and gagpol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. in addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. one such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. we ... | 2011 | 21738476 |
| High-resolution structure of a retroviral protease folded as a monomer. | Mason-Pfizer monkey virus (M-PMV), a D-type retrovirus assembling in the cytoplasm, causes simian acquired immunodeficiency syndrome (SAIDS) in rhesus monkeys. Its pepsin-like aspartic protease (retropepsin) is an integral part of the expressed retroviral polyproteins. As in all retroviral life cycles, release and dimerization of the protease (PR) is strictly required for polyprotein processing and virion maturation. Biophysical and NMR studies have indicated that in the absence of substrates or ... | 2011 | 22101816 |
| the g-patch domain of mason-pfizer monkey virus is a part of reverse transcriptase. | mason-pfizer monkey virus (m-pmv), like some other betaretroviruses, encodes a g-patch domain (gpd). this glycine-rich domain, which has been predicted as an rna binding module, is invariably localized at the 3' end of the pro gene upstream of the pro-pol ribosomal frameshift sequence of genomic rnas of betaretroviruses. following two ribosomal frameshift events and translation of viral mrna, the gpd is present in both gag-pro and gag-pro-pol polyproteins. during maturation of the gag-pro polypr ... | 2011 | 22171253 |
| Rev-Free HIV-1 Gene Delivery System for Targeting Rev-RRE-Crm1 Nucleocytoplasmic RNA Transport Pathway. | The use of RNA transport elements from different viruses can provide novel attributes to HIV-1-based gene delivery systems such as improved safety or Rev independence. We previously described an HIV-1 based gene delivery system that utilized the simian immunodeficiency virus Rev-response element (RRE) in place of the HIV-1 RRE. Despite the use of Rev for the production of vector stocks, we showed the utility of this system for delivery of Rev M10, a dominant-negative mutant of HIV-1 Rev, into T- ... | 2011 | 22164294 |
| localization of nucleoporin tpr to the nuclear pore complex is essential for tpr mediated regulation of the export of unspliced rna. | nucleoporin tpr is a component of the nuclear pore complex (npc) that localizes exclusively to intranuclear filaments. tpr functions as a scaffolding element in the nuclear phase of the npc and plays a role in mitotic spindle checkpoint signalling. export of intron-containing mrna in mason pfizer monkey virus is regulated by direct interaction of cellular proteins with the cis-acting constitutive transport element (cte). in mammalian cells, the transport of gag/pol-cte reporter construct is not ... | 2012 | 22253824 |
| antibodies to retroviruses in recent onset psychosis and multi-episode schizophrenia. | immunological abnormalities involving the upregulation of endogenous retroviruses have been associated with schizophrenia in small studies. | 2012 | 22542615 |
| the structure of myristoylated mason-pfizer monkey virus matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in its membrane binding. | we determined the solution structure of myristoylated mason-pfizer monkey virus matrix protein by nmr spectroscopy. the myristoyl group is buried inside the protein and causes a slight reorientation of the helices. this reorientation leads to the creation of a binding site for phosphatidylinositols. the interaction between the matrix protein and phosphatidylinositols carrying c(8) fatty acid chains was monitored by observation of concentration-dependent chemical shift changes of the affected ami ... | 2012 | 22863803 |
| a cell-based method for screening rna-protein interactions: identification of constitutive transport element-interacting proteins. | we have developed a mammalian cell-based screening platform to identify proteins that assemble into rna-protein complexes. based on tat-mediated activation of the hiv ltr, proteins that interact with an rna target elicit expression of a gfp reporter and are captured by fluorescence activated cell sorting. this "tat-hybrid" screening platform was used to identify proteins that interact with the mason pfizer monkey virus (mpmv) constitutive transport element (cte), a structured rna hairpin that me ... | 2012 | 23133567 |
| sequences within both the 5' utr and gag are required for optimal in vivo packaging and propagation of mouse mammary tumor virus (mmtv) genomic rna. | this study mapped regions of genomic rna (grna) important for packaging and propagation of mouse mammary tumor virus (mmtv). mmtv is a type b betaretrovirus which preassembles intracellularly, a phenomenon distinct from retroviruses that assemble the progeny virion at cell surface just before budding such as the type c human and feline immunodeficiency viruses (hiv and fiv). studies of fiv and mason-pfizer monkey virus (mpmv), a type d betaretrovirus with similar intracellular virion assembly pr ... | 2012 | 23077548 |
| structure of the immature retroviral capsid at 8 å resolution by cryo-electron microscopy. | the assembly of retroviruses such as hiv-1 is driven by oligomerization of their major structural protein, gag. gag is a multidomain polyprotein including three conserved folded domains: ma (matrix), ca (capsid) and nc (nucleocapsid). assembly of an infectious virion proceeds in two stages. in the first stage, gag oligomerization into a hexameric protein lattice leads to the formation of an incomplete, roughly spherical protein shell that buds through the plasma membrane of the infected cell to ... | 2012 | 22722831 |
| interaction of mason-pfizer monkey virus matrix protein with plasma membrane. | budding is the final step of the late phase of retroviral life cycle. it begins with the interaction of gag precursor with plasma membrane (pm) through its n-terminal domain, the matrix protein (ma). however, single genera of retroviridae family differ in the way how they interact with pm. while in case of lentiviruses (e.g., human immunodeficiency virus) the structural polyprotein precursor gag interacts with cellular membrane prior to the assembly, betaretroviruses [mason-pfizer monkey virus ( ... | 2013 | 24478762 |
| a combined marker of inflammation in individuals with mania. | markers of immune activation have been associated with mania but have not been examined in combination. we studied the association between mania and an inflammation score based on four immune markers. | 2013 | 24019926 |
| internet-based crowdsourcing and research ethics: the case for irb review. | the recent success of foldit in determining the structure of the mason-pfizer monkey virus (m-pmv) retroviral protease is suggestive of the power-solving potential of internet-facilitated game-like crowdsourcing. this research model is highly novel, however, and thus, deserves careful consideration of potential ethical issues. in this paper, we will demonstrate that the crowdsourcing model of research has the potential to cause harm to participants, manipulates the participant into continued par ... | 2013 | 23204319 |
| a mason-pfizer monkey virus gag-gfp fusion vector allows visualization of capsid transport in live cells and demonstrates a role for microtubules. | immature capsids of the betaretrovirus, mason-pfizer monkey virus (m-pmv), are assembled in the pericentriolar region of the cell, and are then transported to the plasma membrane for budding. although several studies, utilizing mutagenesis, biochemistry, and immunofluorescence, have defined the role of some viral and host cells factors involved in these processes, they have the disadvantage of population analysis, rather than analyzing individual capsid movement in real time. in this study, we c ... | 2013 | 24386297 |
| determination of protein structure at 8.5å resolution using cryo-electron tomography and sub-tomogram averaging. | cryo-electron tomography combined with image processing by sub-tomogram averaging is unique in its power to resolve the structures of proteins and macromolecular complexes in situ. limitations of the method, including the low signal to noise ratio within individual images from cryo-tomographic datasets and difficulties in determining the defocus at which the data was collected, mean that to date the very best structures obtained by sub-tomogram averaging are limited to a resolution of approximat ... | 2013 | 24184468 |
| shape analysis of the 5' end of the mason-pfizer monkey virus (mpmv) genomic rna reveals structural elements required for genome dimerization. | earlier genetic and structural prediction analyses revealed that the packaging determinants of mason pfizer monkey virus (mpmv) include two discontinuous core regions at the 5' end of its genomic rna. rna secondary structure predictions suggested that these packaging determinants fold into several stem-loops (sls). to experimentally validate this structural model, we employed selective 2' hydroxyl acylation analyzed by primer extension (shape), which examines the flexibility of the rna backbone ... | 2013 | 24152551 |
| gene delivery in a mouse xenograft of a retargeted retrovirus to a solid 143b osteosarcoma. | osteosarcomas are the most common primary bone malignancies found in children and adolescents. an optimized system was developed for efficient retroviral gene delivery into solid 143b osteosarcoma tumors in mice using a retargeted env. in these studies, the viral env cp was isolated from an in vitro screen of a library of feline leukemia virus env randomized in the receptor-binding domain and maintained high titer on human 143b osteosarcoma cell line. | 2013 | 23767896 |
| cost-effective method for the preparation of uniformly labeled myristoylated proteins for nmr measurements. | nuclear magnetic resonance (nmr) is a powerful technique for solving protein structures or studying their interactions. however, it requires molecules labeled with nmr sensitive isotopes like carbon (13)c and nitrogen (15)n. the recombinant expression of labeled proteins is simple to perform but requires quite expensive chemicals. when there is a need for special labeled chemicals, like uniformly (13)c-labeled myristic acid, the price significantly rises. here we describe a cost-effective method ... | 2014 | 24662511 |
| engineered retroviral virus-like particles for receptor targeting. | retroviral gag proteins, as well as fragments minimally containing the capsid (ca) and nucleocapsid (nc) subunits of gag, are able to spontaneously assemble into virus-like particles (vlps). this occurs in mammalian and bacterial cells as well as in in vitro systems. in every circumstance, nucleic acids are incorporated into the forming particles. here, we took advantage of an in vitro system for the generation of non-enveloped mason-pfizer monkey virus (m-pmv) vlps derived from a self-assemblin ... | 2014 | 24132720 |
| crystal structures of beta- and gammaretrovirus fusion proteins reveal a role for electrostatic stapling in viral entry. | membrane fusion is a key step in the life cycle of all envelope viruses, but this process is energetically unfavorable; the transmembrane fusion subunit (tm) of the virion-attached glycoprotein actively catalyzes the membrane merger process. retroviral glycoproteins are the prototypical system to study ph-independent viral entry. in this study, we determined crystal structures of extramembrane regions of the tms from mason-pfizer monkey virus (mpmv) and xenotropic murine leukemia virus-related v ... | 2014 | 24131724 |
| direct evidence for intracellular anterograde co-transport of m-pmv gag and env on microtubules. | the intracellular transport of mason-pfizer monkey virus (m-pmv) assembled capsids from the pericentriolar region to the plasma membrane (pm) requires trafficking of envelope glycoprotein (env) to the assembly site via the recycling endosome. however, it is unclear if env-containing vesicles play a direct role in trafficking capsids to the pm. using live cell microscopy, we demonstrate, for the first time, anterograde co-transport of gag and env. nocodazole disruption of microtubules had differe ... | 2014 | 24418544 |
| stabilization of the β-hairpin in mason-pfizer monkey virus capsid protein- a critical step for infectivity. | formation of a mature core is a crucial event for infectivity of retroviruses such as mason-pfizer monkey virus (m-pmv). the process is triggered by proteolytic cleavage of the polyprotein precursor gag, which releases matrix, capsid (ca), and nucleocapsid proteins. once released, ca assembles to form a mature core - a hexameric lattice protein shell that protects retroviral genomic rna. subtle conformational changes within ca induce the transition from the immature lattice to the mature lattice ... | 2014 | 25365920 |
| gammaretroviral pol sequences act in cis to direct polysome loading and nxf1/nxt-dependent protein production by gag-encoded rna. | all retroviruses synthesize essential proteins via alternatively spliced mrnas. retrovirus genera, though, exploit different mechanisms to coordinate the synthesis of proteins from alternatively spliced mrnas. the best studied of these retroviral, post-transcriptional effectors are the trans-acting rev protein of lentiviruses and the cis-acting constitutive transport element (cte) of the betaretrovirus mason-pfizer monkey virus (mpmv). how members of the gammaretrovirus genus translate protein f ... | 2014 | 25212909 |
| breast cancer-associated protein--a novel binding partner of mason-pfizer monkey virus protease. | we identified breast cancer-associated protein (bca3) as a novel binding partner of mason-pfizer monkey virus (mpmv) protease (pr). the interaction was confirmed by co-immunoprecipitation and immunocolocalization of mpmv pr and bca3. full-length but not c-terminally truncated bca3 was incorporated into mpmv virions. we ruled out the potential role of the g-patch domain, a glycine-rich domain located at the c terminus of mpmv pr, in bca3 interaction and virion incorporation. expression of bca3 di ... | 2014 | 24659101 |
| in vitro assembly of retroviruses. | assembly, part of the late stages of the retroviral life cycle, begins when the structural polyprotein gag associates with viral genomic rna. ultimately, more than a thousand gag molecules form a spherical immature virion. maturation takes place soon after or concomitantly with virus budding and is initiated as gag is cleaved by the retroviral protease into its constituent protein domains. the immature core is thought to disassemble and the liberated ca proteins to reassemble into a morphologica ... | 2014 | 26958734 |
| role of mason-pfizer monkey virus ca-nc spacer peptide-like domain in assembly of immature particles. | the hexameric lattice of an immature retroviral particle consists of gag polyprotein, which is the precursor of all viral structural proteins. lentiviral and alpharetroviral gag proteins contain a peptide sequence called the spacer peptide (sp), which is localized between the capsid (ca) and nucleocapsid (nc) domains. sp plays a critical role in intermolecular interactions during the assembly of immature particles of several retroviruses. published models of supramolecular structures of immature ... | 2014 | 25275119 |
| an sirna screen of membrane trafficking genes highlights pathways common to hiv-1 and m-pmv virus assembly and release. | the assembly and release of retroviruses from the host cells requires a coordinated series of interactions between viral structural proteins and cellular trafficking pathways. although a number of cellular factors involved in retrovirus assembly have been identified, it is likely that retroviruses utilize additional trafficking factors to expedite their assembly and budding that have not yet been defined. we performed a screen using an sirna library targeting host membrane trafficking genes in o ... | 2014 | 25187981 |
| cryo-electron microscopy of tubular arrays of hiv-1 gag resolves structures essential for immature virus assembly. | the assembly of hiv-1 is mediated by oligomerization of the major structural polyprotein, gag, into a hexameric protein lattice at the plasma membrane of the infected cell. this leads to budding and release of progeny immature virus particles. subsequent proteolytic cleavage of gag triggers rearrangement of the particles to form mature infectious virions. obtaining a structural model of the assembled lattice of gag within immature virus particles is necessary to understand the interactions that ... | 2014 | 24843179 |
| rock1 and lim kinase modulate retrovirus particle release and cell-cell transmission events. | the assembly and release of retroviruses from the host cells require dynamic interactions between viral structural proteins and a variety of cellular factors. it has been long speculated that the actin cytoskeleton is involved in retrovirus production, and actin and actin-related proteins are enriched in hiv-1 virions. however, the specific role of actin in retrovirus assembly and release remains unknown. here we identified lim kinase 1 (limk1) as a cellular factor regulating hiv-1 and mason-pfi ... | 2014 | 24696479 |
| the structure of immature virus-like rous sarcoma virus gag particles reveals a structural role for the p10 domain in assembly. | the polyprotein gag is the primary structural component of retroviruses. gag consists of independently folded domains connected by flexible linkers. interactions between the conserved capsid (ca) domains of gag mediate formation of hexameric protein lattices that drive assembly of immature virus particles. proteolytic cleavage of gag by the viral protease (pr) is required for maturation of retroviruses from an immature form into an infectious form. within the assembled gag lattices of hiv-1 and ... | 2015 | 26223638 |
| postentry restriction of mason-pfizer monkey virus in mouse cells. | mason-pfizer monkey virus (m-pmv) is a prototypical betaretrovirus responsible for simian aids (saids) in rhesus macaques. it has been shown previously that mouse cells are resistant to infection by hiv-1 and other primate lentiviruses. however, the susceptibility of mouse cells to primate retroviruses such as m-pmv remains unexplored. in the present study, using single-round green fluorescent protein (gfp) reporter viruses, we showed that various mouse cell lines are unable to support the early ... | 2015 | 25540373 |
| structure of the immature hiv-1 capsid in intact virus particles at 8.8 å resolution. | human immunodeficiency virus type 1 (hiv-1) assembly proceeds in two stages. first, the 55 kilodalton viral gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. second, gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. immature and mature hiv-1 particles are heterogeneous in size and morphology, preventing high-resolution an ... | 2015 | 25363765 |
| roles of the three l-domains in β-retrovirus budding. | retroviral gag protein plays a critical role during the late stage of virus budding and possesses a so-called l-domain containing pt/sap, ppxy, yxxl or fpiv motifs that are critical for efficient budding. mason-pfizer monkey virus (m-pmv) contains psap, pppy, and yadl sequences in gag. this study was performed to investigate the roles of these three l-domain-like sequences in virus replication in three different cell lines, 293t, cos-7 and hela cells. it was found that the ppxy motif plays an es ... | 2015 | 26190584 |
| immune alterations in acute bipolar depression. | immunologic abnormalities have been found in bipolar disorder and acute mania. however, there have been fewer studies of patients with acute bipolar depression. | 2015 | 26061032 |
| resonance assignments of the myristoylated y28f/y67f mutant of the mason-pfizer monkey virus matrix protein. | the matrix protein (ma) of the mason-pfizer monkey virus (m-pmv) plays a key role in the transport and budding of immature retroviral particles from the host cell. natural n-terminal myristoylation of ma is essential for the targeting of the particles to the plasma membrane and participates in the interaction of ma with membranes phospholipids. the mutation y28f/y67f in ma reduces budding and thus causes the accumulation of viral particles under the cytoplasmic membrane. to investigate the impac ... | 2015 | 25773138 |
| molecular aspects of the interaction between mason-pfizer monkey virus matrix protein and artificial phospholipid membrane. | the mason-pfizer monkey virus is a type d retrovirus, which assembles its immature particles in the cytoplasm prior to their transport to the host cell membrane. the association with the membrane is mediated by the n-terminally myristoylated matrix protein. to reveal the role of particular residues which are involved in the capsid-membrane interaction, covalent labelling of arginine, lysine and tyrosine residues of the mason-pfizer monkey virus matrix protein bound to artificial liposomes contai ... | 2016 | 27578150 |
| packaging of mason-pfizer monkey virus (mpmv) genomic rna depends upon conserved long-range interactions (lris) between u5 and gag sequences. | mpmv has great potential for development as a vector for gene therapy. in this respect, precisely defining the sequences and structural motifs that are important for dimerization and packaging of its genomic rna (grna) are of utmost importance. a distinguishing feature of the mpmv grna packaging signal is two phylogenetically conserved long-range interactions (lris) between u5 and gag complementary sequences, lri-i and lri-ii. to test their biological significance in the mpmv life cycle, we intr ... | 2016 | 27095024 |
| nucleic acid binding by mason-pfizer monkey virus ca promotes virus assembly and genome packaging. | the gag polyprotein of retroviruses drives immature virus assembly by forming hexameric protein lattices. the assembly is primarily mediated by protein-protein interactions between capsid (ca) domains and by interactions between nucleocapsid (nc) domains and rna. specific interactions between nc and the viral rna are required for genome packaging. previously reported cryoelectron microscopy analysis of immature mason-pfizer monkey virus (m-pmv) particles suggested that a basic region (residues r ... | 2016 | 26912613 |
| membrane interactions of the mason-pfizer monkey virus matrix protein and its budding deficient mutants. | matrix proteins (mas) play a key role in the transport of retroviral proteins inside infected cells and in the interaction with cellular membranes. in most retroviruses, retroviral mas are n-terminally myristoylated. this modification serves as a membrane targeting signal and also as an anchor for membrane interaction. the aim of this work was to characterize the interactions anchoring retroviral ma at the plasma membrane of infected cell. to address this issue, we compared the structures and me ... | 2016 | 27725181 |
| functional and structural characterization of novel type of linker connecting capsid and nucleocapsid protein domains in murine leukemia virus. | the assembly of immature retroviral particles is initiated in the cytoplasm by the binding of the structural polyprotein precursor gag with viral genomic rna. the protein interactions necessary for assembly are mediated predominantly by the capsid (ca) and nucleocapsid (nc) domains, which have conserved structures. in contrast, the structural arrangement of the ca-nc connecting region differs between retroviral species. in hiv-1 and rous sarcoma virus, this region forms a rod-like structure that ... | 2016 | 27514744 |
| hiv-1 and m-pmv rna nuclear export elements program viral genomes for distinct cytoplasmic trafficking behaviors. | retroviruses encode cis-acting rna nuclear export elements that override nuclear retention of intron-containing viral mrnas including the full-length, unspliced genomic rnas (grnas) packaged into assembling virions. the hiv-1 rev-response element (rre) recruits the cellular nuclear export receptor crm1 (also known as exportin-1/xpo1) using the viral protein rev, while simple retroviruses encode constitutive transport elements (ctes) that directly recruit components of the nxf1(tap)/nxt1(p15) mrn ... | 2016 | 27070420 |
| diverse activities of viral cis-acting rna regulatory elements revealed using multicolor, long-term, single-cell imaging. | cis-acting rna structural elements govern crucial aspects of viral gene expression. how these structures and other posttranscriptional signals affect rna trafficking and translation in the context of single cells is poorly understood. herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral rna regulatory control in individual cells. we apply this strategy to demonstrate differential mrna trafficking behaviors governed by rna elements derived ... | 2017 | 27903772 |
| transcriptional silencing of moloney murine leukemia virus in human embryonic carcinoma cells. | embryonic carcinoma (ec) cells are malignant counterparts of embryonic stem (es) cells and serve as useful models for investigating cellular differentiation and human embryogenesis. though the susceptibility of murine ec cells to retroviral infection has been extensively analyzed, few studies of retrovirus infection of human ec cells have been performed. we tested the susceptibility of human ec cells to transduction by retroviral vectors derived from three different retroviral genera. we show th ... | 2017 | 27795446 |
| optimized method for isolation of immature intracytoplasmic retroviral particles from mammalian cells. | to biochemically and structurally characterize viral intracytoplasmic particles (icaps), a sample of high purity and homogeneity is usually required. production of icaps in the system closely related to their natural host cells is crucial for the analysis of host-cell binding proteins involved in icaps assembly, transport and budding. however, this approach is often hampered by problems with low yield of the icaps due to either low expression or fast release from the host cell. another obstacle ... | 2017 | 28619602 |