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Role of lipids in virus assembly

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195824 Year: Pages: 91 DOI: 10.3389/978-2-88919-582-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology --- Botany
Added to DOAB on : 2016-03-10 08:14:32
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Abstract

RNA enveloped viruses comprise several families belonging to plus and minus strand RNA viruses, such as retroviruses, flavoviruses and orthomyxoviruses. Viruses utilize cellular lipids during critical steps of replication like entry, assembly and egress. Growing evidence indicate important roles for lipids and lipid nanodomains in virus assembly. This special topic covers key aspects of virus-membrane interactions during assembly and egress, especially those of retroviruses and Ebola virus (EBOV). Virus assembly and release involve specific and nonspecific interactions between viral proteins and membrane compartments. Retroviral Gag proteins assemble predominantly on the PM. Despite the great progress in identifying the factors that modulate retroviral Gag assembly on the PM, there are still gaps in our understanding of precise mechanisms of Gag-membrane interactions. Studies over the last two decades have focused on the mechanisms by which other retroviral Gag proteins interact with membranes during assembly. These include human immunodeficiency virus (HIV), Rous sarcoma virus (RSV), equine infectious anemia virus (EIAV), Mason-Pfizer monkey virus (M-PMV), murine leukemia virus (MLV), and human T-lymphotropic virus type (HTLV-1). Additionally, assembly of filoviruses such as EBOV also occurs on the inner leaflet of the PM. The articles published under this special topic highlight the latest understanding of the role of membrane lipids during virus assembly, egress and release.

Keywords

retroviruses --- HIV 1 --- Gag --- Matrix --- membrane --- NMR --- Ebola --- VP40

Manipulation of the host cell by viral auxiliary proteins

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194841 Year: Pages: 118 DOI: 10.3389/978-2-88919-484-1 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2015-11-16 15:44:59
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Abstract

Productive HIV infection requires completion of all the steps of the replication cycle, the success of which largely relying on the multiple interactions established by viral proteins with cellular partners. Indeed, cellular and viral fates are intertwined and this interplay may involve rerouting of cellular factors/pathways to the benefit of the viral life cycle. To gain a foothold into host cells, HIV has to take advantage of available cellular factories and overcome the numerous potential blocks opposed to its replication while ensuring cellular survival. Viral auxiliary proteins are a perfect paradigm to illustrate the complexity of the relationship between HIV and its host. Although these accessory proteins are mostly unnecessary for viral replication in permissive cells in vitro, they play a crucial role in regulating viral spread ex vivo in non-permissive cells and in vivo in hosts. Most accessory proteins are pleiotropic and instrumental in the counteraction of restriction factors and proteins involved in innate immune response. Several proteins of the "intrinsic" immune system that detect the presence of the assailant and initiate a subsequent immune response, as well as restriction factors that are directly devoted to arresting the replication cycle at precise steps have been characterized. Despite the numerous cellular mechanisms dedicated to preventing viral replication, HIV is able to efficiently replicate in humans. Indeed, as a master regulator of cellular machineries and processes, not only has HIV evolved strategies to avoid triggering of pattern recognition receptors, but HIV has also elaborated ways to counteract host restriction factors, thereby overcoming the hurdles that oppose efficient replication. This review collection is dedicated to the manipulation of host cells by HIV-1 and HIV-2, with a particular focus on viral accessory proteins.

Retroviruses, retroelements and their restrictions

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194018 Year: Pages: 127 DOI: 10.3389/978-2-88919-401-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2015-12-10 11:59:06
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Human retroviruses, HIV and HTLV have been recognized as important pathogens because of their association with lethal diseases such as AIDS and ATL. Considerable resources and efforts have been directed at understanding the interaction between these retroviruses and their host which may provide clues as to how the infection can be controlled or prevented. Among the key scientific successes is the identification of intracellular “restriction factors” that have evolved as obstacles to the replication of pathogens including infectious retroviruses. The discovery of APOBEC, which are strong mutagens of retroviral genomes and intracellular retroelements, began a new era of intense research activities into the spectrum of intrinsic anti-HIV activity, leading to the identification of TRIM5a, BST2/Tetherin, and SAMHD1. In response, HIV has evolved several accessory genes as weaponries to evade these intracellular restriction activities. The intracellular antiretroviral defenses evolved in response to endogenous retroelements that make up more than 40% of the entire mammalian genome, and which are regarded as ancestors of infectious retroviruses. LTR-type retroelements are present in all higher eukaryotes, representing about 8% of the human genome. Non-LTR retroelements can be found at extremely high copy numbers also, with a significant portion of mammalin genomes consisting of LINEs. Mammalian genomes are modified by LINEs through insertions, but also by the indirect replication of non-autonomous retrotransposons such as SINEs. LINEs insertion was shown to have played, and continue to play important roles in genomic evolution and somatic genome mosaicism-mediated physiology. And, because retrotransposition can confer genetic diversity that is beneficial to the host, the vertebrate intrinsic immunity has evolved to support a balance between retroelement insertions that confer beneficial and those that cause deleterious gene disruptions. The articles published in this Research Topic should serve not only as valuable references for the field, but provide future topics of research for investigators that should further our understanding of the retrovirus, retroelements and their restrictions.

Keywords

Retrovirus --- Retroelement --- restriction factor --- HIV --- HTLV --- line --- APOBEC --- BST2/Tetherin --- SAMHD1

Carbohydrates: The yet to be tasted sweet spot of immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196258 Year: Pages: 93 DOI: 10.3389/978-2-88919-625-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-08-16 10:34:25
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Carbohydrates are extremely abundant bio-molecules; they are on all mammalian cell surfaces as well as on bacterial cell surfaces. In mammals most secreted proteins are glycosylated, with the glycan component comprising a significant amount by mass of the glycoprotein. Although, many years ago carbohydrate-protein recognition events were demonstrated as involved in invertebrate self-non self recognition, the contribution of carbohydrate-protein binding events to the mechanisms of the mammalian immune response was not embraced with the same enthusiasm. Adaptive immunity and the contribution of antibodies, T cells and T-lymphocyte sub-sets and protein antigen presentation dominated immunological theory. Unlike protein structures, carbohydrate structures are not template driven yet the numerous enzymes involved in carbohydrate biosynthesis and modification are encoded by a major component of the genome, and the expression of these enzymes is tightly regulated. As a consequence carbohydrate structures are also regulated, with different structures appearing according to the stage of cell differentiation and according to the age or health of the individual. The advent of technologies that have allowed carbohydrate structures and carbohydrate-protein binding events to be more easily interrogated has resulted in these types of interactions taking their place in modern immunology. We now know that glycans and their ligands (or lectins) are involved in numerous immunological pathways of both the innate and adaptive systems. However, it is clear that our understanding is still in its infancy, as more and more examples where carbohydrate structures contribute to aspects of the immune response are being recognised. The goal of this research topic is to explore the variety of roles undertaken by glycans and lectins in all aspects of the immune response. The particular focus is how the interactions of glycans with their ligands contribute to the mechanism of immune responses.

Paradigm changes are required in HIV vaccine research

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197279 Year: Pages: 74 DOI: 10.3389/978-2-88919-727-9 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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In his 1962 book "The Structure of Scientific Revolutions", Thomas Kuhn famously argued that researchers in every field of scientific enquiry always operate under a set of presuppositions known as paradigms that are rarely explicitly stated. In the field of HIV vaccine research, several prevailing paradigms led scientists for many years to pursue unfruitful lines of investigations that impeded significant progress. The uncritical acceptance of reigning paradigms makes scientists reluctant to abandon their mistaken assumptions even when they obtain results that are not consistent with the paradigms. The following five paradigms which disregard the degeneracy of the immune system were particularly harmful. 1) There is a primary and intrinsic epitope specific for each B cell receptor and for the corresponding monoclonal antibody.In reality, there is no single, intrinsic or "real" epitope for any antibody but only a diverse group of potential ligands. 2) Reactions with monoclonal antibodies are more specific than the combined reactivity of polyclonal antibodies. In reality, a polyclonal antiserum has greater specificity for a multiepitopic protein because different antibodies in the antiserum recognize separate epitopes on the same protein, giving rise to an additive specificity effect. By focusing vaccine design on single epitope-Mab pairs, the beneficial neutralizing synergy that occurs with polyclonal antibody responses is overlooked. 3) The HIV epitope identified by solving the crystallographic structure of a broadly neutralizing Mab – HIV Env complex should be able, when used as immunogen, to elicit antibodies endowed with the same neutralizing capacity as the Mab. Since every anti HIV bnMab is polyspecific, the single epitope identified in the complex is not necessarily the one that elicited the bnMab. Since hypermutated Mabs used in crystallographic studies differ from their germline-like receptor version present before somatic hypermutation, the identified epitope will not be an effective vaccine immunogen. 4) Effective vaccine immunogenicity can be predicted from the antigenic binding capacity of viral epitopes. Most fragments of a viral antigen can induce antibodies that react with the immunogen, but this is irrelevant for vaccination since these antibodies rarely recognize the cognate, intact antigen and even more rarely neutralize the infectivity of the viral pathogen that harbors the antigen. 5) The rational design of vaccine immunogens using reverse vaccinology is superior to the trial-and-error screening of vaccine candidates able to induce protective immunity. One epitope can be designed to increase its structural complementarity to one particular bnMab, but such antigen design is only masquerading as immunogen design because it is assumed that antigenic reactivity necessarily entails the immunogenic capacity to elicit neutralizing antibodies. When HIV Env epitopes, engineered to react with a bnMab are used to select from human donors rare memory B cells secreting bnAbs, this represents antigen design and not immunogen design. The aim of this Research Topic is to replace previous misleading paradigms by novel ones that better fit our current understanding of immunological specificity and will help HIV vaccine development.

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