Anthea L Hammond

Georgia State University, Atlanta, Georgia, United States

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Publications (8)22.01 Total impact

  • Richard K Plemper, Anthea L Hammond
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    ABSTRACT: Introduction: The measles virus is a major human pathogen responsible for approximately 150,000 deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible, in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence, combined with public anxiety over the vaccination's safety, has led to increased vaccine refusal, especially in Europe. This has led to the resurgence of measles in some areas. Areas covered: This article discusses whether synergizing effective measles therapeutics with the measles vaccination could contribute to finally eradicating measles. The authors identify key elements in a desirable drug profile and review current disease management strategies and the state of experimental inhibitor candidates. The authors also evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics in the management of persistent central nervous system (CNS) viral infection. Finally, the authors contemplate the possible impact of therapeutics in controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles. Expert opinion: Efficacious therapeutics used for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps; this is due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent population, dictates the drug profile. It also has to be safe and efficacious, orally available, shelf-stable at ambient temperature and amenable to cost-effective manufacturing.
    Expert Opinion on Drug Discovery 12/2013; DOI:10.1517/17460441.2014.867324 · 3.47 Impact Factor
  • Richard K. Plemper, Anthea L. Hammond
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    ABSTRACT: Entry of enveloped viruses into cells is initiated by virus binding to a target cell receptor. Subsequent conformational changes in the viral envelope proteins are triggered either by receptor binding or by the low pH of the endosome, depending on the virus family, and facilitate fusion, or merging of the viral and host cell membranes. This allows transfer of the viral genome into the target cell, initiating a new infectious cycle. Inhibitors of viral entry constitute a novel class of antivirals that target discrete steps of this process. Although long-studied for their antiviral potential, entry inhibitors have only recently been brought to market with the licensing of the first-in-class HIV fusion inhibitor T-20 (enfuvirtide, Fuzeon). Entry inhibitors are currently in development against major human and animal pathogens such as HIV, SARS coronavirus, and members of the paramyxovirus family including, amongst others, measles, respiratory syncytial virus (RSV), and Nipah virus. This antiviral class includes antibodies, peptides, and non-peptidic small molecules that act on different steps of the entry process. This review will concentrate on peptidic and non-peptidic inhibitors of viral entry, and describe their mechanisms of action and current development status. Particular emphasis will be given to the development of peptidic and small molecule inhibitors of membrane fusion.
    Anti-Infective Agents in Medicinal Chemistry (Formerly ?Current Medicinal Chemistry - Anti-Infective Agents) 09/2007; 6(4):248-262. DOI:10.2174/187152107782023088
  • Anthea L. Hammond, Richard K. Plemper, Roberto Cattaneo
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    ABSTRACT: Measles virus (MV) replicates preferentially in transformed cells. Its negative strand RNA genome does not integrate or recombine, and its pleomorphic envelope does not impose a rigid upper limit to the size of packaged genomes. To redirect cell entry, replicating MVs have been produced in which the standard attachment protein was replaced by one with an additional specificity domain. Specificity domains as diverse as a growth factor or a single chain antibody are able to confer entry through targeted receptors. MV mutants with reduced or ablated binding to the natural receptors are being produced, and may have applications in different oncolytic therapies.
    Vector Targeting for Therapeutic Gene Delivery, 03/2003: pages 321 - 336; , ISBN: 9780471234302
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    ABSTRACT: To understand the molecular determinants of measles virus (MV) cytopathicity, we have characterized mutant viruses exhibiting a more-extensive cell-to-cell fusion while maintaining efficient replication to high titers. A virus which is modified by the addition of an 8-amino-acid Flag epitope tag at the cytoplasmic tail of its H (for MV hemagglutinin) envelope glycoprotein replicates efficiently, has an increased cytopathicity, possesses a greater infectivity per particle, and has an altered protein composition compared with that of unmodified MV. The mutant phenotype is not specifically linked to the epitope sequence, since an alternatively added HA (for influenza virus-derived hemagglutinin) epitope tag caused similar effects. We demonstrate that both epitope tags weaken the interaction between the H and fusion (F) glycoproteins in virus-infected cells. This reduction in strength of H/F interaction is independent of the presence of the viral matrix (M) protein. Viruses with this less stable complex are more sensitive to neutralization by a soluble octameric form of the CD46 receptor, consistent with their increased fusogenicity. Similar analyses of glycoproteins derived from MV strains with reduced cytopathicities confirm that the strength of H and F glycoprotein interaction is a modulator of viral fusogenicity.
    Journal of Virology 06/2002; 76(10):5051-61. DOI:10.1128/JVI.76.10.5051-5061.2002 · 4.65 Impact Factor
  • Richard K Plemper, Anthea L Hammond
    Progress in molecular and subcellular biology 02/2002; 29:61-84.
  • R K Plemper, A.L. Hammond, R Cattaneo
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    ABSTRACT: The endoplasmic reticulum (ER) was investigated as the initial oligomerization site for the envelope glycoproteins H and F of measles virus (MV), a clinically relevant member of the Paramyxoviridae family, and consequences of this interaction for viral replication were studied. Both proteins were tagged at their cytosolic tails with RRR and KKXX motifs, respectively, resulting in their efficient retention in the ER. Co-transfection of the retained constructs with transport competent MV glycoproteins revealed a dominant negative effect on their biological activity indicating intracellular complex formation and thus retention. Pulse-chase analysis and co-immunoprecipitation experiments demonstrated that this effect is based on both homo- and hetero-oligomerization in the ER. Recombinant viruses additionally expressing ER-retained F showed an altered cytopathic phenotype accompanied by greatly reduced particle release. Similar mutant viruses additionally expressing ER-retained H could not be rescued indicating an even greater negative effect of this protein on virus viability. Our study suggests that both homo- and hetero-oligomerization of MV glycoproteins occur in the ER and that these events are of significance for early steps of particle assembly.
    Journal of Biological Chemistry 12/2001; 276(47):44239-46. DOI:10.1074/jbc.M105967200 · 4.57 Impact Factor
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    ABSTRACT: To redirect the tropism of the vaccine strain of measles virus (MV), Edmonston B, to a targeted cell population, we displayed on the viral hemagglutinin (H) a single-chain antibody (scAb) specific for the tumor-associated carcinoembryonic antigen (CEA). We generated H fusion proteins with three forms of the scAb appended, differing in the lengths of the linkers separating the VH and VL domains and thus in the oligomerization states of the scAbs. All proteins were stable, appeared properly folded, and were transported to the cell surface, but only H displaying the long-linker form of scAb was functional in supporting cell-cell fusion. This protein induced extensive syncytia in cells expressing the normal virus receptor CD46 and also in CD46-negative cells expressing the targeted receptor, human CEA. Replication-competent MV with H replaced by H displaying the long-linker form of scAb was recovered and replicated efficiently in both CD46-positive and CD46-negative, CEA-positive cells. Thus, MV not only tolerates the addition of a scAb on its H protein but also infects cells via a novel interaction between the scAb and its targeted receptor.
    Journal of Virology 04/2001; 75(5):2087-96. DOI:10.1128/JVI.75.5.2087-2096.2001 · 4.65 Impact Factor
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    R K Plemper, A L Hammond, R Cattaneo
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    ABSTRACT: Attachment of measles virus (MV) to its cellular receptor is mediated by the viral envelope glycoprotein hemagglutinin (H). H exists at the viral surface as a disulfide-linked dimer which may associate into a tetramer. We aimed to define regions of H essential for its homo-oligomerization. To delineate these more precisely, we have generated a series of H ectodomain truncation mutants and studied their abilities to form both homotypic complexes and heterotypic complexes with full-length H. We define a "minimal unit" which is sufficient for MV H dimerization as that encompassing residues 1 to 151. This unit forms both homodimers and heterodimers with full-length H protein, although neither is transported to the cell surface even in the presence of other MV proteins. We show that cysteine residues at positions 139 and 154 are both critical in mediating covalent dimerization, not only of the truncated H mutants but also of full-length MV H protein. Even those cysteine mutants unable to form covalent intermolecular interactions are biologically active, mediating the formation of syncytia, albeit at a reduced rate. We demonstrate that this impaired capacity to mediate cell-to-cell fusion is based mainly on a reduced transport rate of the mutant molecules to the cell surface, indicating a role for covalent intermolecular interactions in efficient transport of MV H dimers to the cell surface.
    Journal of Virology 08/2000; 74(14):6485-93. DOI:10.1128/JVI.74.14.6485-6493.2000 · 4.65 Impact Factor

Publication Stats

302 Citations
22.01 Total Impact Points


  • 2013
    • Georgia State University
      • Center for Inflammation, Immunity and Infection
      Atlanta, Georgia, United States
  • 2003
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States