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Contribution Of Innate Responses To Viral Control In Hiv 1 Infection
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Book Synopsis Contribution of Innate Responses to Viral Control in HIV-1 Infection by : Persephone Borrow
Download or read book Contribution of Innate Responses to Viral Control in HIV-1 Infection written by Persephone Borrow and published by Frontiers Media SA. This book was released on 2020 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Human Immunodeficiency Virus by : Emilio Emini
Download or read book The Human Immunodeficiency Virus written by Emilio Emini and published by Princeton University Press. This book was released on 2021-04-13 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: The past few years have witnessed an explosive increase in our collective knowledge of the biology of the human immunodeficiency virus (HIV). Researchers have acquired new understanding of the virus's biochemistry, molecular biology, pathogenesis, genetics, and immunobiology. Resulting therapeutic advances have significantly prolonged the lives of thousands. Yet, the need to develop better therapies is ever more acute and--given the virus's continued spread through the human population--the need for an effective vaccine is urgent. These goals can be accomplished only through the experienced synthesis of information from the many disciplines participating in HIV research and through the insights of new investigators. This volume is designed to lower the barriers imposed on investigators by the sheer volume of available information--information that often can be found only in far-flung and specialized journals. It provides, in a single resource, an in-depth overview of the diverse areas that constitute HIV research. The result is a broad introduction for students and researchers new to the field as well as an integrated overview for researchers specialized in particular areas of HIV investigation. The volume will also benefit those seeking technical understanding of the virus's biology, including physicians treating HIV-infected patients. Each chapter is a comprehensive presentation of one area of current AIDS research--including work on the virus life cycle, epidemiology, genetics, protease and reverse transcriptase inhibitors, receptor and co-receptor interactions, therapeutic targets, clinical treatment, immunobiology, and vaccines--written by a leading researcher in that area. The contributors are Jon P. Anderson, Jan Balzarini, Elana Cherry, Thomas J. Coates, Chris Collins, Jon H. Condra, Mark B. Feinberg, Richard B. Gaynor, Matthias Götte, Daria J. Hazuda, Spyros Kalams, Nathaniel R. Landau, Gerald H. Learn, Norman L. Letvin, James I. Mullins, Willscott E. Naugler, David Nickle, Matthew Rain, Allen G. Rodrigo, Daniel Shriner, Shalom Spira, Mario Stevenson, Todd Summers, Catherine Ulich, Joseph P. Vacca, Mark A. Wainberg, Bruce D. Walker, and Yang Wang.
Book Synopsis Control of Innate Antiviral Immunity by HIV-1 by : Arjun Rustagi
Download or read book Control of Innate Antiviral Immunity by HIV-1 written by Arjun Rustagi and published by . This book was released on 2013 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus 1 (HIV-1) infection continues to be a major public health problem, with 34 million people infected worldwide. Cell-intrinsic innate immune defenses are essential for the control of HIV-1 infection but are subverted by the virus to establish successful infection. Interferon regulatory factor 3 (IRF3) is a central transcription factor of innate immune signaling that is activated by cellular pattern recognition receptors in response to the presence of non-self molecules (e.g. viral RNA or DNA). Activation of IRF3 induces the expression of antiviral and immunomodulatory genes whose products can suppress HIV-1 infection within target cells and regulate the adaptive immune response to infection. We have found that during acute infection HIV-1 evades innate antiviral immunity through the actions of HIV-1 viral protein u (Vpu), which interacts with IRF3 and inhibits its activity. While HIV infection eventually results in proteolytic destruction of IRF3 at later time points of acute infection, we found that inhibition of IRF3-dependent IFN-[Beta] transcription by Vpu occurs at early time points. In addition, Vpu blocked both IRF3- and NF[kappa]B-dependent activities at the IFN-[Beta] promoter. These findings led us to hypothesize that Vpu blocks IRF3 activation to prevent IRF3 from carrying out the necessary biochemical steps to drive antiviral gene expression. We investigated the process of Vpu regulation of IRF3, and found that IRF3 and Vpu form a stable complex during infection of CD4+ T cells with HIV-1. Using truncation and deletion mutants of recombinant IRF3, we mapped the binding epitope for Vpu on IRF3 to a region of IRF3 protein called the IRF association domain. This domain is the site necessary for homodimerization of IRF3 molecules after activation and interaction with transcriptional cofactors. Thus, we hypothesized that Vpu alters IRF3 dimerization and cofactor interaction. Indeed, when we examined the IRF3 activation pathway in the presence of Vpu to identify the site of the Vpu-induced block in IRF3 activity, we found that Vpu inhibited IRF3 dimerization and CBP binding. We predict that Vpu antagonism of IRF3-directed innate immunity is a key step in HIV-1 pathogenesis during acute infection. Further, IRF3 depletion and control of innate antiviral immunity by HIV-1 may correlate with disease progression in HIV-infected patients. To test these predictions, we have developed two novel monoclonal antibodies to human IRF3 to support the study of IRF3 activation and HIV-mediated IRF3 depletion among patient samples in a high-throughput manner. One of these antibodies, AR-1, is specific for activated IRF3. The other, AR-2, detects total IRF3 levels in a flow cytometric assay of blood leukocytes. Use of these new antibodies to study IRF-3 levels during HIV infection could reveal an innate immune correlate of HIV-1 disease progression, while studies to fully define the interaction between Vpu and IRF3 may reveal novel targets for the development of drugs that preserve IRF3 activity during HIV-1 infection.
Book Synopsis Janeway's Immunobiology by : Kenneth Murphy
Download or read book Janeway's Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Book Synopsis Chimpanzees in Biomedical and Behavioral Research by : National Research Council
Download or read book Chimpanzees in Biomedical and Behavioral Research written by National Research Council and published by National Academies Press. This book was released on 2011-12-05 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: For many years, experiments using chimpanzees have been instrumental in advancing scientific knowledge and have led to new medicines to prevent life-threatening and debilitating diseases. However, recent advances in alternate research tools have rendered chimpanzees largely unnecessary as research subjects. The Institute of Medicine, in collaboration with the National Research Council, conducted an in-depth analysis of the scientific necessity for chimpanzees in NIH-funded biomedical and behavioral research. The committee concludes that while the chimpanzee has been a valuable animal model in the past, most current biomedical research use of chimpanzees is not necessary, though noted that it is impossible to predict whether research on emerging or new diseases may necessitate chimpanzees in the future.
Book Synopsis Persistent Viral Infections by : R. Ahmed
Download or read book Persistent Viral Infections written by R. Ahmed and published by Wiley-Blackwell. This book was released on 1999 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Book Synopsis The Cytokine Network by : Frances R. Balkwill
Download or read book The Cytokine Network written by Frances R. Balkwill and published by Frontiers in Molecular Biology. This book was released on 2000 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cytokines are soluble mediators of intercellular communication. They contribute to a chemical signalling language that regulates development, tissue repair, haemopoiesis, inflammation and the immune response. Potent cytokine polypepides have pleiotropic activities and functional redundancy.They act in a complex network where one cytokine can influence the production of, and response to, many other cytokines. In the past five years, this bewildering array of more than 100 effector molecules and associated cell surface receptors has been simplified by study of cytokine and cytokinereceptor structure; elucidation of convergent intracellular signalling pathways; and molecular genetics, and targeted gene disruption to 'knock-out' production of individual cytokines in mice. It is also now clear that the pathophysiology of infectious, autoimmune and malignant disease can bepartially explained by the induction of cytokines and the subsequent cellular response. Viral homologues exist for many cytokines and receptors and genetic variations in cytokine production may influence response to pathogenic stimuli. Cytokine and cytokine antagonists have shown therapeuticpotential in a number of chronic and acute diseases. The Cytokine Network: Frontiers in Molecular Biology is not a survey of individual cytokines, but guides the reader through the latest research on the cytokine network as a whole covering genomics, signalling pathways, control of the immuneresponse, and therapeutics.
Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.
Book Synopsis Fenner and White's Medical Virology by : Christopher J. Burrell
Download or read book Fenner and White's Medical Virology written by Christopher J. Burrell and published by Academic Press. This book was released on 2016-11-09 with total page 604 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fenner and White's Medical Virology, Fifth Edition provides an integrated view of related sciences, from cell biology, to medical epidemiology and human social behavior. The perspective represented by this book, that of medical virology as an infectious disease science, is meant to provide a starting point, an anchor, for those who must relate the subject to clinical practice, public health practice, scholarly research, and other endeavors. The book presents detailed exposition on the properties of viruses, how viruses replicate, and how viruses cause disease. These chapters are then followed by an overview of the principles of diagnosis, epidemiology, and how virus infections can be controlled. The first section concludes with a discussion on emergence and attempts to predict the next major public health challenges. These form a guide for delving into the specific diseases of interest to the reader as described in Part II. This lucid and concise, yet comprehensive, text is admirably suited to the needs of not only advanced students of science and medicine, but also postgraduate students, teachers, and research workers in all areas of virology. Features updated and expanded coverage of pathogenesis and immunity Contains the latest laboratory diagnostic methods Provides insights into clinical features of human viral disease, vaccines, chemotherapy, epidemiology, and control
Book Synopsis Host-virus Interactions by : Diane Singhroy
Download or read book Host-virus Interactions written by Diane Singhroy and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The innate immune system is the first line of defence against HIV, activated within minutes of transmission. HIV must replicate and diversify fast enough to overcome the harsh environment it faces within its target immune cells. The enormous selective pressure that the immune system exercises on replicating HIV species would favor certain phenotypes that permit HIV to replicate despite intrinsic immune factors. Importantly, drug resistance mutations have been shown to be archived and to re-emerge rapidly when failing treatments are re-initiated. It is widely established that resting memory CD4+ T-lymphocytes represent an important latent reservoir for HIV. Monocytes and macrophage also contribute to the latent reservoir. In addition, monocytes can infiltrate and differentiate in tissues where they reside for decades. They can also penetrate into privileged drug sanctuary sites and they are largely resistant to the cytopathic effects of HIV infection. Wild type (WT) HIV-1 have difficulty infecting dendritic cells (DC), monocytes, macrophage and resting CD4+ T-cells in part because of an intrinsic immune factor called SAMHD1 that keeps dNTP pool low, thus limiting the availability of this substrate for HIV reverse transcription. Previous work in our laboratory has demonstrated that HIV-1 reverse transcriptase (RT) enzyme harboring specific drug resistance mutations (DRMs) can overcome low dNTP compared to WT. This led us to hypothesis that such DRMs, specifically E138K, may help the virus to overcome SAMHD1 restriction and to replicate better in the above mentioned immune cells.The research I performed during my thesis is divided in 3 parts. First I studied PRMT6 and arginine methylation which we consider to be part of the intrinsic immune system. We had previously showed in the laboratory that PRMT6 is able to restrict HIV replication. My work centered on the regulation of PRMT6 through automethylation that I characterized and demonstrated that PRMT6 automethylation is crucial for its stability and anti-HIV activity. The second intrinsic immune factor I studied was SAMHD1 where I looked at the replication profile of different drug resistant mutants in primary immune cells and cell lines that express or not SAMHD1. I did in fact find that different drug resistant viruses grew differently in different cell types. Most remarkably, some of the single mutants replicate better in DC and resting CD4+ T-cells whereas E138K mutant replicate as well as the WT virus in macrophages.We extended our study to integrase drug resistant mutants given that selection studies in cord blood mononuclear cells indicated that cell types might influence the genotype that are selected for under the integrase inhibitor dolutegravir (DTG) pressure. We found that R263K- and H51Y/R263K-containing HIV replicated better than WT in resting CD4+ T-cells. This showed both RT and IN drug resistant viruses have improved fitness in specific cells. Drug resistant virus emerging from long-lived reservoir immune cells could also contribute to the chronic immune activation that is seen in some patients. " --
Book Synopsis Handbook on Immunosenescence by : Tamas Fulop
Download or read book Handbook on Immunosenescence written by Tamas Fulop and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 1693 pages. Available in PDF, EPUB and Kindle. Book excerpt: This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.
Book Synopsis Host-control of HIV by : Lisa van Pul
Download or read book Host-control of HIV written by Lisa van Pul and published by . This book was released on 2024 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Infection with HIV-1 is characterized by a gradual decline in CD4 T cells as well as chronic activation of the immune system. The balance between an adequate immune response on one side and overstimulation and immune dysfunction on the other, influences the highly variable disease course of untreated HIV-1 infection. Current antiretroviral therapy suppresses viral replication efficiently however, it does not completely restore the immune system and some level of immune activation and inflammation persists. Understanding the mechanisms of HIV-1 pathogenesis could provide novel avenues for treatment of HIV-1 infection and restoration of the observed immune imbalance. In this thesis, the immune response to HIV-1 infection in relation to disease progression and disease control is explored at the level of both the innate and the adaptive immune response. The findings of this thesis contribute to expanding our knowledge on the immune response to HIV-1 infection."--
Book Synopsis Models of Protection Against HIV/SIV by : Gianfranco Pancino
Download or read book Models of Protection Against HIV/SIV written by Gianfranco Pancino and published by Academic Press. This book was released on 2011-11-02 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: A successful vaccine for the prevention and/or immunotherapy against HIV/AIDS is one of the prominent challenges of the 21st century. To date, all human vaccine trials against this virus/disease have resulted in failure, or at best have shown very low efficacy. The scientific community dealing with HIV/AIDS has unanimously proposed a focus on basic science, with the intention of identifying correlates of protection that can serve as guides in developing and evaluating vaccine preparation. However, Nature seems to have already found several ways of dealing with infections by HIV and related primate lentiviruses, either by resisting infection or, once infected, avoiding immune damage and immunodeficiency. Models of Protection Against HIV/SIV will allow for an in-depth reflection on the perspectives for vaccine and therapy research derived from important recent studies. It will be authored by some of the most well known specialists in the field of HIV resistance/protection: including F. Barré-Sinoussi (2008 Nobel Prize for Medicine winner), B. Walker, S. Rowland-Jones, A. Telenti, M. Lederman and F. Plummer. This book is structured in a unique way, looking at three models of resistance/protection separately and then comparing the models against one another to provide its readership with a detailed examination of the research that is most predominant in the search for a vaccine. This structure presents the information in an easy-to-understand format and gives the book a cross-discipline appeal -- an important reference for those in the scientific community, medical care, public health and academia alike. - Provides extensive descriptions and comparisons on the different models of protection agains HIV/AIDS - Comprehensive writing and illustrations - Contributors are among the most eminent specialists in the field
Book Synopsis HIV-1 Tat Induced Immune Responses and Its Effect on Opportunistic Infections by : Chi-Him Pong
Download or read book HIV-1 Tat Induced Immune Responses and Its Effect on Opportunistic Infections written by Chi-Him Pong and published by . This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "HIV-1 Tat Induced Immune Responses and Its Effect on Opportunistic Infections" by Chi-him, Pong, 龐智謙, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Acquired immunodeficiency syndrome (AIDS) is a major problem in our current society. There are over 35 million of the population that are currently living with human immunodeficiency virus (HIV), and the number of HIV-infected patients are still rising every year in spite of our efforts to control it. Furthermore, within the AIDS affected population, opportunistic infection is a major cause of complications and is the number one cause of death. The HIV trans-activator (Tat) protein plays a major role in the AIDS pathogenesis. HIV-1 Tat is known to cause dysregulation of cytokines such as TNF-α, IL-6, and IL-10 in AIDS patients. In this study we recognized a proto-oncogene, c-Myc, could regulate the cytokine dysregulation caused by HIV-1 Tat in primary blood monocyte derived macrophages (PBMac). By knocking down the expression of c-Myc with gene specific small-interfering RNA (siRNA), we demonstrated that c-Myc may be critical for the expression of the pro-inflammatory cytokines TNF-α and IL-6. HIV-1 Tat was subsequently found to regulate the expression of c-Myc via the activation of dsRNA-activated protein kinase (PKR), ERK1/2 and p38 mitogen-activated protein kinase (MAPK). Furthermore, c-Myc regulation of the pro-inflammatory cytokines was demonstrated to have a role in AIDS related opportunistic infections. HIV-1 Tat was shown to increase the intracellular growth of Mycobacteria avium complex (MAC) within PBMac. This increase in MAC growth was in turn found to be regulated by TNF-α expression controlled by c-Myc. HIV-1 Tat was also demonstrated to induce the expression of RIG-I, a common pattern recognition receptor of double stranded RNA viruses, in PBMac. RIG-I is known to activate the viral immune responses such as the type-I interferon (IFN) and pro-inflammatory cytokine pathways. This induction of RIG-I by HIV-1 Tat was found to be regulated by c-Myc, as well as through other signalling kinases such as p38 MAPK and PKR. Tat induction of RIG-I ultimately led to the induction of IFN-α2 and IFN-β through the expression and nuclear translocation of the interferon regulatory factor-7 (IRF-7). This alteration in type-I IFN expression regulated by HIV-1 Tat and RIG-I was also found to play a role against AIDS related opportunistic infections. HIV-1 Tat is known to increase the infectivity of Kaposi's sarcoma-related herpesvirus (KSHV), a common opportunistic viral infection. We were able to demonstrate that this increase in KSHV infectivity was regulated by RIG-I and type-I IFN induced by HIV-1 Tat. Lastly, this study also demonstrated how HIV-1 Tat was able to manipulate the expression of IL-8 induced by KSHV in PBMac. HIV-1 Tat was able to mediate the production of IL-8 induced by KSHV by altering the phosphorylation of the p38 MAPK and the signal transducer and activator of transcription-1 (STAT-1). Taken together, the results of this study showed how c-Myc and RIG-I may be able to play critical roles in HIV-1 Tat induced cytokine dysregulation. Furthermore, the importance of these pathways is further demonstrated in their roles in regulating the immune responses against opportunistic infections in AIDS patients. DOI: 10.5353/th_b5334861 Subjects: HIV infections Viral proteins
Download or read book HIV-1 Latency written by Guido Silvestri and published by Springer. This book was released on 2018-10-11 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.
Book Synopsis Investigating the Characteristics of HIV-1 Envelope in the Context of Simian-human Immunodeficiency Virus by : Anna Catherine Smith
Download or read book Investigating the Characteristics of HIV-1 Envelope in the Context of Simian-human Immunodeficiency Virus written by Anna Catherine Smith and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV-1, the etiologic agent of AIDS, continues to be a challenge to global public health. There is no practical cure for HIV-1 infection and the development of a preventive vaccine remains a priority. The simian-human immunodeficiency virus (SHIV)/macaque model is a valuable tool for HIV-1 preclinical vaccine studies. However, the model is limited by its ability to faithfully recapitulate diverse, transmitted HIV-1 Envelope (Env) proteins, the key antigenic target for preventative vaccines. Due to macaque innate immune barriers to infection, development of infectious SHIVs requires adaptation to their host, a process that introduces viral mutations and alters the original antigenic profile of the Env protein. A small subset of SHIVs has been successfully adapted for high levels of replication through serial passage in macaques. The process of in vivo passage in macaques, passage in cell culture, in vitro and in vivo selection, as well as structure-guided design have added to our knowledge of SHIV adaptation to macaque. However, further mechanistic studies to define the characteristics of Envs that mediate robust infection of macaques are needed to shed light on the viral and host factors necessary for the generation of SHIVs that retain the antigenic profiles of diverse, transmitted HIV-1 Env while also establishing persistent infection in macaques. Transmitted HIV-1 Envs must overcome intrinsic barriers as well as the host innate immune response, which is most active in the acute stage of infection. By identifying the minimal adaptive changes necessary to overcome the macaque innate immune response, infectious SHIVs that retain antigenic similarity to HIV-1 transmitted viruses can be designed for vaccine studies. Recent work has identified the env gene as the determinant of increased replication and type-I interferon in adapted SHIVs and here we discuss the identification of two potential N-linked glycosylation sites as the molecular determinants of type-I interferon resistance and increased replication in an Env isolated early in infection. Further, we define the characteristics conferred by these glycan mutants as well as their impact on a family of anti-viral interferon stimulated genes (ISG), the interferon- stimulated transmembrane proteins (IFITMs). The CD4 receptor is the entry receptor used by both HIV-1 and simian immunodeficiency viruses (SIVs). However, a single amino acid difference between human and macaque CD4 reduces the efficacy by which SHIVs encoding HIV-1 Env are able to mediate entry into macaque CD4+ T cells. Mutations previously identified in the HIV-1 Env gp120 and gp41 subunits that improve usage of rhesus macaque CD4 are evaluated here for improved fusion and replication in macaque cells, thus improving our understanding of the intrinsic barrier of CD4 usage and its contribution to improving replication of SHIVs encoding minimally altered HIV-1 Envs for vaccine preclinical trials. By investigating the ISGs that restrict unadapted SHIVs, exploring the role of glycosylation, and evaluating Env conformation, we improve our understanding of the host-virus interaction, adaptation to the innate immune response, and help inform the rational design of SHIVs that encode relevant transmitted Envs by identifying minimal changes that allow for improved viral replication. By evaluating several mutations in HIV- 1 Env that improve SHIV replication and fusion, described here, future structural studies of Envs encoding these mutations may guide design of SHIVs that retain HIV-1 Env structure and antigenic profile yet establish persistent infection in macaques.
