A5018160359- HIV Research and Treatment
- RNA Research and Splicing
- Virology and Viral Diseases
- interferon and immune responses
- Herpesvirus Infections and Treatments
- RNA and protein synthesis mechanisms
- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS drug development and treatment
- Animal Virus Infections Studies
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Viral Infections and Immunology Research
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- vaccines and immunoinformatics approaches
- Cellular transport and secretion
- RNA regulation and disease
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Enzyme Structure and Function
- Blood groups and transfusion
- Animal Disease Management and Epidemiology
- Hepatitis C virus research
- Viral Infections and Vectors
Rockefeller University
2014-2025
Howard Hughes Medical Institute
2011-2023
Aaron Diamond AIDS Research Center
2004-2016
Miami University
2001
The expression of many putative antiviral genes is upregulated when cells encounter type I interferon (IFN), but the actual mechanisms by which IFN-induced gene products inhibit virus replication are poorly understood. A recently identified antiretroviral protein, termed tetherin (previously known as BST-2 or CD317), blocks release nascent human immunodeficiency 1 (HIV-1) particles from infected cells, and an HIV-1 accessory Vpu, acts a viral antagonist tetherin. Here, we show that capable...
Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist tetherin. Here, we show positive selection evident in primate tetherin sequences Vpu appears to have specifically adapted antagonize variants found humans chimpanzees. Tetherin rhesus macaques (rh), African green monkeys (agm) mice were able inhibit particle release, but resistant...
Highlights•ISG screening identifies direct and indirect antiretroviral proteins•Interferon-γ inhibits HIV-1 through IDO1-mediated tryptophan depletion•TRIM56 enhances the potential of interferon-αSummaryInterferons (IFNs) exert their anti-viral effects by inducing expression hundreds IFN-stimulated genes (ISGs). The activity known ISGs is insufficient to account for IFN, suggesting that with are yet be described. We constructed an arrayed library from rhesus macaques tested ability...
Retroviral late-budding (L) domains are required for the efficient release of nascent virions. The three known types L domain, designated according to essential tetrapeptide motifs (PTAP, PPXY, or YPDL), each bind distinct cellular cofactors. We and others have demonstrated that recruitment an ESCRT-I subunit, Tsg101, a component class E vacuolar protein sorting (VPS) machinery, is budding viruses, such as human immunodeficiency virus type 1 (HIV-1) Ebola virus, encode PTAP-type but...
ABSTRACT Myxovirus resistance 2 (Mx2/MxB) has recently been uncovered as an effector of the anti-HIV-1 activity type I interferons (IFNs) that inhibits HIV-1 at early stage postinfection, after reverse transcription but prior to proviral integration into host DNA. The mechanistic details Mx2 antiviral are not yet understood, a few substitutions in capsid have shown confer Mx2. Through combination vitro evolution and unbiased mutagenesis, we further map determinants sensitivity reveal...
Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures inactivate tetherin, with prototype being HIV-1 Vpu protein. Here we show human herpesvirus Kaposi's sarcoma-associated (KSHV) sensitive to tetherin restriction and its activity counteracted by KSHV encoded RING-CH E3 ubiquitin ligase K5. expression in KSHV-infected cells particle release, as does depletion K5...
HIV-1 accesses the nuclear DNA of interphase cells via a poorly defined process involving functional interactions between capsid protein (CA) and nucleoporins (Nups). Here, we show that CA can bind multiple Nups, both natural manipulated variation in Nup levels impacts infection manner is strikingly dependent on cell-type, cell-cycle, cyclophilin A (CypA). We also Nups mediate function antiviral MX2, MX2 variably inhibit non-viral NLS function. Remarkably, enhancing inhibiting effects...
Tetherin (Bst2/CD317/HM1.24) is an interferon-induced antiviral host protein that inhibits the release of many enveloped viruses by tethering virions to cell surface. The HIV-1 accessory protein, Vpu, antagonizes through a variety proposed mechanisms, including surface downregulation and degradation. Previous studies have demonstrated mutation transmembrane domains (TMD) both Vpu affect antagonism, but it not known whether bind directly each other. Here, we use cysteine-scanning mutagenesis...
Tetherin/BST2 is a type-II membrane protein that inhibits the release of range enveloped viruses, including HIV-1. Here we report three crystal structures human tetherin, full-length ectodomain, triple cysteine mutant and an ectodomain truncation. These show tetherin forms continuous alpha helix encompassing almost entire ectodomain. Tetherin helices dimerize into parallel coiled coils via interactions throughout C-terminal portion A comparison multiple dimer reveals inherent constrained...
ABSTRACT Cell surface glycosaminoglycans (GAGs), in particular heparan sulfate (HS), have been proposed to mediate the attachment of human immunodeficiency virus type 1 (HIV-1) target cells prior entry, and both viral gp120 envelope protein virion-associated cyclophilin A (CypA) shown directly interact with HS its analogues. To determine role GAGs HIV infection, we generated HIV-susceptible derivatives CHO cell lines that either express high levels (CHO-K1) or lack (pgsA745). Using a panel...
All retroviruses package cellular RNAs into virions. Studies of murine leukemia virus (MLV) revealed that the major host cell encapsidated by this simple retrovirus were LTR retrotransposons and noncoding (ncRNAs). Several classes ncRNAs appeared to be packaged MLV shortly after synthesis, as precursors tRNAs, small nuclear RNAs, nucleolar all enriched in To determine extent which human immunodeficiency (HIV-1) packages similar we used high-throughput sequencing characterize within...
Viruses employ a variety of strategies to escape or counteract immune responses, including depletion cell surface major histocompatibility complex class I (MHC-I), that would ordinarily present viral peptides CD8+ cytotoxic T cells. As part screen elucidate biological activities associated with individual severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins, we found ORF7a reduced MHC-I levels by approximately fivefold. Nevertheless, in cells infected SARS-CoV-2, were even...
The Rev Response Element (RRE) forms an oligomeric complex with the viral protein to facilitate nuclear export of intron-retaining RNAs during late phase HIV-1 infection. However, our structural understanding this crucial virological process remains limited. In study, we determined several crystal structures intact RRE stem-loop II in two distinct conformations, performed negative-staining electron microscopy and molecular dynamics simulations, revealed that three-way junction RNA exhibits...
Glyoxalase II participates in the cellular detoxification of cytotoxic and mutagenic 2-oxoaldehydes. Because its role chemical detoxification, glyoxalase has been studied as a potential anti-cancer and/or anti-protozoal target; however, very little is known about active site reaction mechanism this important enzyme. To characterize kinetic enzyme, detailed mutational study Arabidopsis was conducted. Data presented here demonstrate for first time that cytoplasmic form contains an iron-zinc...