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Disclosure Within HIV-Affected Families

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455263 Year: Pages: 130 DOI: 10.3389/978-2-88945-526-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Public Health
Added to DOAB on : 2019-01-23 14:53:42
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While HIV/AIDS is a global public heath challenge, its impact is arguably greatest in the Sub-Saharan Africa (SSA), where new infections account for approximately 66% of the total number of HIV-positive persons globally. In SSA, medical, social, and economic resources are limited, thus necessitating innovative approaches to disease prevention. One of the mechanisms of prevention that is most promising occurs through HIV disclosure to family members (e.g., adult sexual partners) generally, and to children in particular. Our emphasis in this eBook is on HIV disclosure to children because it has multiple benefits, including improved adherence to antiretroviral medication treatment and understanding at an early age of the impact of sexual activity on the spread of HIV. While there is a noticeable gap in research on HIV disclosure to younger children, some of the general reasons for non-disclosure include concerns about fear of adult partners leaving relationships, and that children are too young to comprehend the severity of the situation and may tell others outside the family. Thus, it is critical to better understand how the HIV disclosure process happens (or does not happen) within HIV-affected families, as well as the best practices on how to disclose. In this eBook, we present a combination of empirical research studies and critical literature reviews that investigate the reasons for and for not disclosing HIV status within HIV-affected families and provide evidence-based practices that could be adopted by healthcare professionals to help HIV-positive parents facilitate disclosure activities within these families. This information can also be used by researchers, practitioners, and stakeholders who are in a position to influence policies on effective HIV disclosure practices, guidelines, and programs.

Why vaccines to HIV, HCV and Malaria have so far failed - Challenges to developing vaccines against immunoregulating pathogens

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199662 Year: Pages: 157 DOI: 10.3389/978-2-88919-966-2 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology --- Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-01-19 14:05:46
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Despite continuous progress in the development of anti-viral and anti-bacterial/parasite drugs, the high cost of medicines and the potential for re-infection, especially in high risk groups, suggest that protective vaccines to some of the most dangerous persistent infections are still highly desirable. There are no vaccines available for HIV, HCV and Malaria, and all attempts to make a broadly effective vaccine have failed so far. In this Research Topic we look into why vaccines have failed over the years, and what we have learn from these attempts. Rather than only showing positive results, this issue aims to reflect on failed efforts in vaccine development. Coming to understand our limitations will have theoretical and practical implications for the future development of vaccines to these major global disease burdens.

Keywords

Vaccine --- Infectious Disease --- HIV --- HCV --- Malaria --- influenza --- immunology --- Genetics

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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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

HIV-Induced Damage of B Cells and Production of HIV Neutralizing Antibodies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454617 Year: Pages: 171 DOI: 10.3389/978-2-88945-461-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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Multiple dysfunctions take place in the B cell compartment during HIV-1 infection, comprising depletion of resting memory B cells carrying serological memory to vaccines and previously met pathogens. In addition, population of B cells characterized by the expression of exhaustion markers are enlarged during HIV-1 infection. Antibodies with the capacity to neutralize a broad range of HIV-1 isolates can be detected only in a minority of infected patients, after a year or more from acute infection. An open question is whether the inability of producing neutralizing HIV-1 antibodies is somehow linked to the B cell immunopathology observed in patients. In this research topic we invited scientists to summarize the current state of knowledge on regulation and development of B cells and antibody responses during HIV-1 infection; fifteen contributions were received comprising both reviews and original articles. The articles are related to B cell dysfunctions identified in HIV-1 infected individuals, production of different types of antibodies (neutralizing versus non neutralizing, and of different isotypes) in vivo during HIV-1 infection and the biological factors which may impact on this process, clinical potential and applications of anti-HIV antibodies and how to achieve neutralizing antibody responses to HIV-1 epitopes upon vaccination. The topic has gathered articles on front-line research undertaken in the field of B cells and antibodies in HIV-1 infection. It is our hope that the collection of articles presented in this book may be useful for new and experienced scholars in the field and add a piece to the complex puzzle of knowledge needed for the development of an HIV-1 vaccine.

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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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.

Neuroimmune Interface in Health and Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453788 Year: Pages: 174 DOI: 10.3389/978-2-88945-378-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology --- Neurology
Added to DOAB on : 2018-11-16 17:17:57
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It is now well appreciated that the immune system, in addition to its traditional role in defending the organism against pathogens, communicate in a well-organized fashion with the brain to maintain homeostasis and regulate a set of neural functions. Perturbation in this brain-immune interactions due to inflammatory responses may lead to psychiatric and neurological disorders. Microglia are one of the essential cells involved in the brain-immune interactions. Microglial cells are now not simply regarded as resident tissue macrophages in the brain. These cells are derived from myeloid progenitor cells in the yolk sac in early gestation, travel to the brain parenchyma and interact actively with neurons during the critical period of neurogenesis. Microglia provide a trophic support to developing neurons and take part in the neural wiring through the activity-dependent synapse elimination via direct neuron-microglia interactions. Altered microglial functions including changes in the gene expression due to early life inflammatory events or psychological and environmental stressors can be causally related to neurodevelopmental diseases and mental health disorders. This type of alterations in the neural functions can occur in the absence of infiltration of inflammatory cells in the brain parenchyma or leptomeninges. In this sense, the pathogenetic state underlying a significant part of psychiatric and neurological diseases may be similar to “para-inflammation”, an intermediate state between homeostatic and classical inflammatory states as defined by Ruslan Medzhitov (Nature 454:428-35, 2008). Therefore, it is important to study how systemic inflammation affects brain health and how local peripheral inflammation induces changes in the brain microenvironment. Chronic pain is also induced by disturbance in otherwise well-organized multisystem interplay comprising of reciprocal neural, endocrine and immune interactions. Especially, early-life insults including exposure to immune challenges can alter the neuroanatomical components of nociception, which induces altered pain response later in life. Recently the discrete roles of microglia and blood monocyte-derived macrophages are being defined. The distinction may be further highlighted by disorders in which the brain parenchymal tissue is damaged. Therefore, studies investigating the dynamics of immune cells in traumatic brain injury and neurotropic viral infections including human immunodeficiency virus, etc. as well as neurodegenerative diseases such as amyotrophic lateral sclerosis are promising to clarify the interplay between the central nervous and immune systems. The understanding of the histological architecture providing the infrastructure of such neuro-immune interplay is also essential. This Frontiers research topic brings together fourteen articles and aims to create a platform for researchers in the field of psychoneuroimmunology to share the recent theories, hypotheses and future perspectives regarding open questions on the mechanisms of cell-cell interactions with chemical mediators among the nervous, immune and endocrine systems. We hope that this platform would reveal the relevance of the studies on multisystem interactions to enhance the understanding of the mechanisms underlying a wide variety of neurological and psychiatric disorders.

Macromolecular Structure Underlying Recognition in Innate Immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455270 Year: Pages: 151 DOI: 10.3389/978-2-88945-527-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:42
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Immune molecules have evolved to distinguish “self “molecules from “non-self”, “altered self” and “danger” molecules. Recognition is mediated via interactions between pattern recognition receptor molecules (PPRs) and their ligands, which include hydrophobic and electrostatic interactions between amino acid residues on the PPRs and uncharged or charged groups on amino acid residues, sugar rings or DNA/RNA molecules. Recognition in innate immunity range from cases (C1q, mannin-binding protein etc) where recognition is orchestrated by interaction between many ligands with one receptor molecule, and density of interaction is necessary for strong specific recognition, distinct from weak non-specific binding, and cases such as TLRs and NLRs where recognition involves complexation of single receptor and ligand, followed by oligomerisation of the receptor molecule. The majority of PPR molecules bind and recognise a wide variety of ligands, e.g TLR4 recognises LPS (gram negative bacteria), Lipotechoic acid (gram positive bacteria), heat shock protein hsp60, respiratory syncytial virus fusion protein etc, molecules that are structurally dissimilar to each other. This indicates considerable flexibility in their binding domains (amino acid residue variations) and modes (hydrophobic and charged, direct or mediated via an adaptor molecule). However, in many cases there is a dearth of structural and molecular data available, required to delineate the mechanism of ligand binding underlining recognition in pathogen receptors in innate immunity. Insights into requirements of conformation, charge, surface etc in the recognition and function of innate immunity receptors and their activation pathways, based on current data can suggest valuable avenues for future work.

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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