10 results on '"Maury, Wendy"'
Search Results
2. Selective Infection of Human CD4+ Cells by Simian Immunodeficiency Virus: Productive Infection Associated with Envelope Glycoprotein-Induced Fusion
- Author
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Koenig, Scott, Hirsch, Vanessa M., Olmsted, Robert A., Powell, Douglas, Maury, Wendy, Rabson, Arnold, Fauci, Anthony S., Purcell, Robert H., and Johnson, Philip R.
- Published
- 1989
3. HIV-1 Infection of First-Trimester and Term Human Placental Tissue: A Possible Mode of Maternal-Fetal Transmission [with Discussion]
- Author
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Maury, Wendy, Potts, Barbara J., and Rabson, Arnold B.
- Published
- 1989
4. TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis.
- Author
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Brunton, Bethany, Rogers, Kai, Phillips, Elisabeth K., Brouillette, Rachel B., Bouls, Ruayda, Butler, Noah S., and Maury, Wendy
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EBOLA virus ,VESICULAR stomatitis ,VIRUS diseases ,PATHOGENIC viruses ,T cells ,HEPATITIS A virus cellular receptors - Abstract
Background: T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection. Methodology/Principal findings: Infectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor
-/- mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of virus infection. Conclusions: Our studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
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5. Drug induced superinfection in HIV and the evolution of drug resistance
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Leontiev, Vladimir V., Maury, Wendy J., and Hadany, Lilach
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HIV , *DRUG resistance , *VIRAL disease treatment , *AIDS treatment , *VIRUSES , *ANTIVIRAL agents - Abstract
Abstract: The rapid evolution of HIV drug resistance is a major cause of AIDS treatment failure. Superinfection, the infection of an already infected cell by additional virions, can be a major factor contributing to the evolution of drug resistance. However, the pattern and consequences of superinfection in HIV populations are far from fully understood. In this paper we study the implications of the fact that superinfection is regulated by HIV. We propose that superinfection is negatively associated with the success of the virus, so that more successful viruses are less likely to allow superinfection. We use computational models to investigate the effect that regulated superinfection would have on the evolution of drug resistance in HIV population. We find that regulated, fitness-associated superinfection can provide a distinct advantage to the virus in adapting to anti-HIV drugs in comparison with unregulated superinfection. Based on the results of the computational models and on current biological evidence, we suggest that the mechanism of fitness-associated regulation of coinfection in HIV is plausible, and that its investigation can lead to new ways to fight viral drug resistance. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
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6. Cellular specificity of HIV-1 replication can be controlled by LTR sequences
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Reed-Inderbitzin, Edward and Maury, Wendy
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TROPISMS , *IMMUNODEFICIENCY , *VIRUSES - Abstract
Two well-established determinants of retroviral tropism are envelope sequences that regulate entry and LTR sequences that can regulate viral expression in a cell-specific manner. Studies with human immunodeficiency virus-1 (HIV-1) have demonstrated that tropism of this virus maps primarily to variable envelope sequences. Studies have demonstrated that T cell and macrophage-specific transcription factor binding motifs exist in the upstream region of the LTR U3; however, the ability of the core enhancer/promoter proximal elements (two NF-κB and three Sp1 sites) to function well in macrophages and T cells have led many to conclude that HIV LTR sequences are not primary determinants of HIV tropism. To determine if cellular specificity could be imparted to HIV by the core enhancer elements, the enhancer/promoter proximal region of the HIV LTR was substituted with motifs that control gene expression in a myeloid-specific manner. The enhancer region from equine infectious anemia virus (EIAV) when substituted for the HIV enhancer/promoter proximal region was found to drive expression in a macrophage-specific manner and was responsive to HIV Tat. The addition of a 5′ methylation-dependent binding site (MDBP) and a promoter proximal Sp1 motif increased expression without altering cellular specificity. Spacing between the promoter proximal region and the TATA box was also found to influence LTR activity. Infectivity studies using chimeric LTRs within the context of a dual-tropic infectious molecular clone established that these LTRs directed HIV replication and production of infectious virions in macrophages but not primary T cells or T cell lines. This investigation demonstrates that cellular specificity can be imparted onto HIV-1 replication at the level of viral transcription and not entry. [Copyright &y& Elsevier]
- Published
- 2003
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7. Characterization of a Cytolytic Strain of Equine Infectious Anemia Virus.
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Maury, Wendy, Wright, Patrick J., and Bradley, Sarahann
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EQUINE infectious anemia , *VIRUSES - Abstract
A novel strain of equine infectious anemia virus (EIAV) called vMA-1c that rapidly and specifically killed infected equine fibroblasts (ED cells) but not other infectible cell lines was established. This strain was generated from an avirulent, noncytopathic strain of EIAV, MA-1. Studies with this new cytolytic strain of virus have permitted us to define viral parameters associated with EIAV-induced cell killing and begin to explore the mechanism, vMA-1c infection resulted in induction of rapid cell death, enhanced fusogenic activity, and increased rates of spread in equine fibroblasts compared to other strains of EIAV. The highly cytolytic nature of vMA-1c suggested that this strain might be superinfecting equine fibroblasts. Receptor interference studies demonstrated that prior infection of equine fibroblasts with EIAV did not alter the ability of vMA-1c to infect and kill these cells. In similar studies in a canine fibroblast cell line, receptor interference did occur, vMA-1c infection of equine fibroblasts was also associated with large quantities of unintegrated viral DNA, a well-established hallmark of retroviral superinfection. Cloning of the vMA-1c genome identified nucleotide changes that would result in at least one amino acid change in all viral proteins. A chimeric infectious molecular clone containing the vMA-1c tat, S2, and env open reading frames recapitulated most of the characteristics of vMA-1c, including superinfection, fibroblast killing, and fusogenic activity. In summary, in vitro selection for a strain of EIAV that rapidly killed cells resulted in the generation of a virus that was able to superinfect these cells, presumably by the use of a novel mechanism of cell entry. This phenotype mapped to the 3' half of the genome. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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8. TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions
- Author
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Moller-Tank, Sven, Lovell, William, Maury, Wendy, Lemon, Stanley M., Hensley, Lucinda, Misumi, Ichiro, Das, Anshuman, Hirai-Yuki, Asuka, Cullen, John M., González-López, Olga, Whitmire, Jason K., Brouillette, Rachel, and Rhein, Bethany
- Subjects
viruses ,3. Good health - Abstract
Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1 −/− Ifnar1 −/− and Tim4 −/− Ifnar1 −/− double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1 −/− mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1 −/− Ifnar1 −/− mice compared to Ifnar1 −/− mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. IMPORTANCE T cell immunoglobulin and mucin-containing domain protein 1 (TIM1) was reported more than 2 decades ago to be an essential cellular receptor for hepatitis A virus (HAV), a picornavirus in the Hepatovirus genus, resulting in its designation as “hepatitis A virus cellular receptor 1” (HAVCR1) by the Human Genome Organization Gene Nomenclature Committee. However, recent studies have shown that HAV exists in nature as both naked, nonenveloped (HAV) virions and membrane-cloaked, quasi-enveloped infectious virus (eHAV), prompting us to revisit the role of TIM1 in viral entry. We show here that TIM1 (HAVCR1) is not an essential cellular receptor for HAV entry into cultured cells or required for viral replication and pathogenesis in permissive strains of mice, although it may facilitate early stages of infection by binding phosphatidylserine on the eHAV surface. This work thus corrects the published record and sets the stage for future efforts to identify specific hepatovirus entry factors.
9. A Naturally Occurring Polymorphism in the Base of Sudan Virus Glycoprotein Decreases Glycoprotein Stability in a Species-Dependent Manner.
- Author
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Lennemann, Nicholas J., Dillard, Jacob, Ruggio, Natalie, Cooney, Ashley L., Schaack, Grace A., Davey, Robert A., and Maury, Wendy
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EBOLA virus , *VIRUSES , *HIGH temperatures , *TRANSGLUTAMINASES , *GLUTAMINE , *FILOVIRIDAE - Abstract
Sudan virus (SUDV) is one of five filoviruses that compose the genus Ebolavirus that has been responsible for episodic outbreaks in Central Africa. While the SUDV glycoprotein (GP) structure has been solved, GP residues that affect SUDV entry have not been extensively examined; many of the entry characteristics of SUDV GP are inferred from studies with the Zaire Ebola virus (EBOV) GP. Here, we investigate the effect on virus entry of a naturally occurring polymorphism in SUDV GP. Two of the earliest SUDV isolates contain glutamine at residue 95 (Q95) within the base region of GP1, whereas more recent SUDV isolates and GPs from all other ebolaviruses carry lysine at this position (K95). A K95Q change dramatically decreased titers of pseudovirions bearing SUDV GP, whereas the K95Q substitution in EBOV GP had no effect on titer. We evaluated virus entry to identify SUDV GP Q95-specific entry defects. The presence of Q95 in either EBOV or SUDV GP resulted in enhanced sensitivity of GP to proteolytic processing, yet this could not account for the SUDV-specific decrease in GP Q95 infectivity. We found that SUDV GP Q95 pseudovirions were more sensitive to imipramine, a GP-destabilizing antiviral. In contrast, SUDV GP K95 was more stable, requiring elevated temperatures to inhibit virus infection. Thus, the residue present at GP 95 has a critical role in stabilizing the SUDV glycoprotein, whereas this polymorphism has no effect on EBOV GP stability. These results provide novel insights into filovirus species-specific GP structure that affects virus infectivity. IMPORTANCE Filovirus outbreaks are associated with significant morbidity and mortality. Understanding the structural constraints of filoviral GPs that control virus entry into cells is critical for rational development of novel antivirals to block infection. Here, we identify a naturally occurring glutamine (Q) to lysine (K) polymorphism at residue 95 as a critical determinant of Sudan virus GP stability but not Zaire Ebola virus GP stability. We propose that glutamine at residue 95 in Sudan virus GP mediates decreased virus entry, thereby reducing infectivity. Our findings highlight a unique structural characteristic of Sudan virus GP that affects GP-mediated functionality. Further, it provides a cautionary note for the development of future broadspectrum filovirus antivirals. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
10. The Tyro3 Receptor Kinase Axl Enhances Macropinocytosis of Zaire Ebolavirus.
- Author
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Hunt, Catherine L., Kolokoltsov, Andrey A., Davey, Robert A., and Maury, Wendy
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CELL membranes , *GLYCOPROTEINS , *VIRUSES , *RNA , *DEXTRAN - Abstract
Axl, a plasma membrane-associated Tyro3/Axl/Mer (TAM) family member, is necessary for optimal Zaire ebolavirus (ZEBOV) glycoprotein (GP)-dependent entry into some permissive cells but not others. To date, the role of Axl in virion entry is unknown. The focus of this study was to characterize entry pathways that are used for ZEBOV uptake in cells that require Axl for optimal transduction and to define the role of Axl in this process. Through the use of biochemical inhibitors, interfering RNA (RNAi), and dominant negative constructs, we demonstrate that ZEBOV-GP-dependent entry into these cells occurs through multiple uptake pathways, including both clathrin-dependent and caveola/lipid raft-mediated endocytosis. Other dynamin-dependent and -independent pathways such as macropinocytosis that mediate high-molecular-weight dextran uptake also stimulated ZEBOV-GP entry into these cells, and inhibitors that are known to block macropinocytosis inhibited both dextran uptake and ZEBOV infection. These findings provided strong evidence for the importance of this pathway in filovirus entry. Reduction of Axl expression by RNAi treatment resulted in decreased ZEBOV entry via macropinocytosis but had no effect on the clathrin-dependent or caveola/lipid raft-mediated endocytic mechanisms. Our findings demonstrate for the first time that Axl enhances macropinocytosis, thereby increasing productive ZEBOV entry. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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