DOCSLIB.ORG

Phenotypic Characteristics of Mucosally Transmitted HIV-1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Phenotypic Characteristics of Mucosally Transmitted HIV-1 University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2013 Phenotypic Characteristics of Mucosally Transmitted HIV-1 Nicholas F. Parrish University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Molecular Biology Commons, and the Virology Commons Recommended Citation Parrish, Nicholas F., "Phenotypic Characteristics of Mucosally Transmitted HIV-1" (2013). Publicly Accessible Penn Dissertations. 684. https://repository.upenn.edu/edissertations/684 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/684 For more information, please contact [email protected]. Phenotypic Characteristics of Mucosally Transmitted HIV-1 Abstract Mucosal transmission accounts for the majority of new human immunodeficiency virus type 1 (HIV-1) infections and results in a genetically and phenotypically homogenous founder virus population in 60-80 percent of cases. Biological properties common to these transmitted and founder (T/F) viruses but not chronic control (CC) viruses would define ek y targets for microbicides and vaccines. To identify such properties, we tested 45 T/F and 52 CC envelope glycoproteins (Envs) from the best studied and most prevalent HIV-1 subtypes (B and C, respectively) in various pseudotype assays to determine their receptor and coreceptor interaction, tropism for primary CD4+ T cell subsets, and sensitivity to neutralizing antibodies. T/F Envs were unable to mediate entry into cells expressing low amounts of CD4, thus macrophages and other CD4low cells likely do not support their replication during mucosal transmission. In contrast, T/F Env pseudoviruses efficiently infected primary memory CD4+ T cells with a preference for the effector rather than central memory subset, as did CC pseudoviruses. There was a trend towards increased sensitivity of T/F viruses to neutralization by antibodies targeting the CD4 binding site. All T/F Envs were able to use the coreceptor CCR5 for cell entry, whereas some CC Envs used CXCR4 alone. However, one bona fide T/F virus entered and replicated very poorly in CCR5+ cells in vitro, so efficient use of CCR5 as tested is not absolutely required for transmission. To extend these studies beyond intrinsic Env functions, we characterized the Env content, infectivity, dendritic cell interaction, and interferon alpha (IFN-α) sensitivity of 27 T/F and 14 CC infectious molecular clones from subtypes B and C. T/F viruses contained more Env and were more infectious than CC viruses. T/F viruses also readily attached to DCs and were effectively transferred to CD4+ T cells. T/F viruses were more resistant to the inhibitory effect of IFN-α on virus spread than CC viruses, suggesting that selective pressure imposed by the innate immune response may in part mediate the bottleneck associated with mucosal transmission. Future work is needed to define the mechanistic basis of these phenomena in order to target them to prevent HIV-1 transmission. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Cell & Molecular Biology First Advisor Beatrice H. Hahn Subject Categories Molecular Biology | Virology This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/684 PHENOTYPIC CHARACTERISTICS OF MUCOSALLY TRANSMITTED HIV-1 Nicholas F. Parrish A DISSERTATION in Cell and Molecular Biology Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2013 Supervisor of Dissertation _____________________ Beatrice H. Hahn Professor of Medicine and Microbiology Graduate Group Chairperson ________________________ Daniel S. Kessler, Associate Professor, Department of Cell and Developemental Biology Dissertation Committee: Robert W. Doms, Chair and Pathologist-in-Chief, Children’s Hospital of Philadelphia James A. Hoxie, Professor of Medicine Ronald G. Collman, Professor of Medicine Scott E. Hensley, Assistant Professor, The Wistar Institute DEDICATION This dissertation is dedicated to the memory of Matthias H. Kraus, M.D., an artisan of molecular biology. He discovered ERBB3, which is the topic of over 1000 peer-reviewed publications and the target of monoclonal antibodies under clinical development as cancer therapeutics. His tutelage was a provident gift. It is solely to his credit if I lack any of the bad habits of a retrovirologist. ii ACKNOWLEDGMENT I thank my mentor Dr. Beatrice Hahn. It has been an honor to sit at the feet of such an accomplished scientist. She directed me to important problems and made sure I stayed focused on them, somehow without limiting my perceived creativity and freedom. She has encouraged me when I needed encouragement and challenged me when I needed to be challenged. The support she has provided seemed limitless. Most critically, her desire for me to improve as a scientist has been unrelenting; I sincerely hope that will continue. Dr. George Shaw has done more than anyone other than Dr. Hahn to improve the environment of my training. His perspective on HIV, especially that from “5,000 feet,” is unparalleled. I have also gained an undeserved benefactor in Dr. Robert Doms. In the same way that Dr. Shaw is the master of defining the big question, Dr. Doms is the ultimate authority on the proper manner(s) of addressing the question. I would not have withstood the challenges of the endeavor this dissertation represents without the careful sculpting of my undergraduate mentor, Dr. Bruce Levin. I am honored to share what I do of his approach and hermeneutics. I had the pleasure of receiving training and airing ideas in several external labs. The six weeks I spent at Penn in Dr. Doms’ lab prior to our move were easily the most productive of my entire four years in terms of data generation. Dr. Craig Wilen, my closest collaborator and friend, had more to do with that than I did. Dr. Nina Bhardwaj at NYU, along with Dr. Meagan O’Brien, hosted me for my first trip to dendritic cell mecca and taught me tissue culture techniques important for this work. Dr. Feng Gao allowed me to train with his group at Duke and was a critical collaborator entrusting me with many reagents his lab spent countless hours generating. Dr. Ben Greenbaum and Dr. Arnold Levine at the Institute for Advanced Studies listened to my speculation with the interest normally reserved for data, helping refine some of the hypotheses tested here. iii Committee members Dr. James Hoxie, Dr. Ronald Collman, and Dr. Scott Hensley provided exponentially more useful guidance than would be predicted based on the number of our meetings. Those to whom I am sincerely grateful for direct guidance and assistance include: Dr. Jesus Salazar-Gonzalez, a yeoman with whom I shared many late evenings in Birmingham, and Maria Salazar. Dr. Brandon Keele, who has thought more and more clearly on this topic than anyone except Dr. Hahn and Dr. Shaw. Dr. Hui Li, Dr. Fredric Bibollet-Ruche, Julie Decker, Juliet Easlick, Dr. Yingying Li, and Dr. Weimin Liu, each true professionals who patiently suffered through teaching an amateur their techniques. Fellow students in Dr. Hahn’s, Dr. Shaw’s, and Dr. Doms’ labs including Dr. Rebecca Rudicell, Dr. Rui Kong, Dr. Joshua Baalwa, Michael Lopker, Mark Stoddard, Shilpa Iyer, Dr. Jason Wojcechowskyj, Josiah Peterson, Chuka Didigu, Sesh Sundararaman, and Hannah Barbian provided helpful discussions. I especially thank my parents, who nurtured my scientific leaning from an early age and along with my in-laws continue to support my long training. I am especially proud of my dad’s blessing to pursue research and my mom’s unconditional conviction that I am great at it. Because of my passion to answer the questions raised in this work, my lifestyle over the past four years has been distinct from what I would have imagined, and with foresight and self-control, perhaps even chosen. Thus my wife Erica’s steadfast commitment to me, extending even to the same scientific pursuit, warrants gratitude and accolades for which this is not the venue. I cannot imagine a better colleague. iv ABSTRACT PHENOTYPIC CHARACTERISTICS OF MUCOSALLY TRANSMITTED HIV-1 Nicholas F. Parrish Beatrice H. Hahn Mucosal transmission accounts for the majority of new human immunodeficiency virus type 1 (HIV-1) infections and results in a genetically and phenotypically homogenous founder virus population in 60-80 percent of cases. Biological properties common to these transmitted and founder (T/F) viruses but not chronic control (CC) viruses would define key targets for microbicides and vaccines. To identify such properties, we tested 45 T/F and 52 CC envelope glycoproteins (Envs) from the best studied and most prevalent HIV-1 subtypes (B and C, respectively) in various pseudotype assays to determine their receptor and coreceptor interaction, tropism for primary CD4+ T cell subsets, and sensitivity to neutralizing antibodies. T/F Envs were unable to mediate entry into cells expressing low amounts of CD4, thus macrophages and other CD4low cells likely do not support their replication during mucosal transmission. In contrast, T/F Env pseudoviruses efficiently infected primary memory CD4+ T cells with a preference for the effector rather than central memory subset, as did CC pseudoviruses. There was a trend towards increased sensitivity of T/F viruses to neutralization by antibodies targeting the CD4 binding site. All T/F Envs were able to use the coreceptor CCR5 for cell entry, whereas some CC Envs used CXCR4 alone. However, one bona fide T/F virus entered and replicated very poorly in CCR5+ cells in vitro, so efficient use of CCR5 as tested is not absolutely required for transmission. To extend these studies beyond intrinsic Env functions, we characterized the Env content, infectivity, dendritic cell interaction, and interferon alpha (IFN-α) sensitivity of 27 T/F and 14 CC infectious molecular clones from subtypes B and C. T/F viruses contained more Env and were more infectious than CC viruses.
Load more

Recommended publications
  • Frequency and Implications of HIV Superinfection
    Review Frequency and implications of HIV superinfection Andrew D Redd, Thomas C Quinn, Aaron A R Tobian* HIV superinfection occurs when an individual with HIV is infected with a new distinct HIV viral strain. Superinfection Published Online has been reported throughout the world, and studies have recorded incidence rates of 0–7∙7% per year. Use of next- May 31, 2013 generation sequencing has improved detection of superinfection, which can be transmitted by injecting drug use and http://dx.doi.org/10.1016/ S1473-3099(13)70066-5 sexual intercourse. Superinfection might have incidence rates comparable to those of initial HIV infection. Clinicians Division of Intramural should encourage safe sexual and injecting drug use practices for HIV-infected patients because superinfection has Research, National Institute of detrimental eff ects on clinical outcomes and could pose a concern for large-scale antiretroviral treatment plans. The Allergy and Infectious Diseases, occurrence of superinfection has implications for vaccine research, since it seems initial HIV infection is not fully National Institutes of Health, protective against a subsequent infection. Additional collaborative research could benefi t care of patients and inform Bethesda, MD, USA (A D Redd PhD, future vaccine design. Prof T C Quinn MD); Department of Pathology, Introduction Detection of HIV superinfection School of Medicine, Johns HIV superinfection occurs when an individual with The investigators in initial studies that identifi ed indi- Hopkins University, Baltimore, MD (A A R Tobian MD) HIV becomes infected with a new, phylogenetically distinct viduals dually infected with HIV-1 and HIV-2 used Correspondence to: viral HIV strain.
    [Show full text]
  • Coevolution of HIV-1 and Broadly Neutralizing Antibodies
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Curr Opin Manuscript Author HIV AIDS. Author Manuscript Author manuscript; available in PMC 2020 October 13. Published in final edited form as: Curr Opin HIV AIDS. 2019 July ; 14(4): 286–293. doi:10.1097/COH.0000000000000550. Coevolution of HIV-1 and broadly neutralizing antibodies Nicole A. Doria-Rosea, Elise Landaisb aVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland bIAVI Neutralizing Antibody Center, Immunology and Microbiology Department, The Scripps Research Institute, La Jolla, California, USA Abstract Purpose of review—Exploring the molecular details of the coevolution of HIV-1 Envelope with broadly neutralizing antibodies (bNAbs) in infected individuals over time provides insights for vaccine design. Since mid-2017, the number of individuals described in such publications has nearly tripled. New publications have extended such studies to new epitopes on Env and provided more detail on previously known sites. Recent findings—Studies of two donors – one of them an infant, the other with three lineages targeting the same site – has deepened our understanding of V3-glycan-directed lineages. A V2- apex-directed lineage showed remarkable similarity to a lineage from a previously described donor, revealing general principles for this class of bNAbs. Understanding development of CD4 binding site antibodies has been enriched by the study of a VRC01-class lineage. Finally, the membrane-proximal external region is a new addition to the set of epitopes studied in this manner, with early development events explored in a study of three lineages from a single donor.
    [Show full text]
  • Lessons from Viral Superinfections for HIV-1 Vaccine Design Stephanie Jost* Ragon Institute of MGH, MIT and Harvard, USA
    C S & lini ID ca A l f R o e l s Journal of a e n a r r Jost, J AIDS Clinic Res 2013, S3 c u h o J DOI: 10.4172/2155-6113.S3-005 ISSN: 2155-6113 AIDS & Clinical Research Review Article Open Access Lessons from Viral Superinfections for HIV-1 Vaccine Design Stephanie Jost* Ragon Institute of MGH, MIT and Harvard, USA Abstract Superinfection refers to a second viral infection in the context of a pre-existing adaptive immune response to prior infection with a viral strain that has not been cleared, the two viruses being genetically distinct yet belonging to the same genus. As such, this phenomenon provides unique settings to gain insights into the immune correlates of protection against HIV-1. The focus of this review is to discuss the current knowledge about immune responses to HIV-1 and to other viruses that are associated with partial or complete immunity to superinfection, or lack thereof, and how that could be applied to future HIV-1 vaccine strategies. Keywords: HIV-1; Superinfection; Vaccine; Co-infection; Viral HIV-1 Rapid Evolution and Diversity: A Challenge for infection; Recombination Vaccine Design Introduction The extremely rapid evolution of the virus probably largely contributed to the failure or limited success of HIV-1 vaccines evaluated The human immunodeficiency virus type 1 (HIV-1) affects 34 to date [5]. HIV-1’s extensive genetic diversity was first brought to light million adults and children worldwide, and the ongoing spread of the around 1983, when full-length sequences of the virus became available, epidemic resulted in about 2.5 million new infections and 1.7 million and has since then expanded [6].
    [Show full text]
  • Using Knowledge of HIV Status As an HIV Prevention Strategy
    From Prevention in Focus, Spring 2014 Unknown, negative or positive? Using knowledge of HIV status as an HIV prevention strategy By James Wilton and Tim Rogers As front-line workers in HIV prevention, it is important to understand what prevention strategies clients are using and how they understand the risks associated with them. A common HIV prevention strategy used by gay men and other men who have sex with men (MSM) is known as “serosorting” and involves limiting all – or just “high-risk” – sexual activities to partners who have the same HIV status. For example, an HIV-negative person may choose to only have condomless sex with other people who are HIV negative or an HIV-positive person may choose to only have condomless sex with other people who are HIV positive. This strategy is used in the context of different types of relationships, such as stable, casual, monogamous and non-monogamous relationships. This article focuses on how often serosorting is used, how well it works, and how knowledge of HIV status can be effectively used as a prevention strategy. The article only covers serosorting strategies that are based on individuals identifying themselves or others as HIV-positive or HIV-negative. It does not address other factors, such as viral load or use of other HIV prevention strategies, which play a very important role in assessing HIV risk. For information on these other strategies, please see the resource list at the end of the article. How common is serosorting? Serosorting is quite common among MSM in Canada and other parts of the world.
    [Show full text]
  • Modelling the Role of Amelioration and Drug Lords on Drug Epidemics and the Impact of Substance Abuse on the Dynamics of HIV/AIDS
    Modelling the Role of Amelioration and Drug Lords on Drug Epidemics and the Impact of Substance Abuse on the Dynamics of HIV/AIDS by Hatson John Boscoh Njagarah Thesis presented in partial fulfilment of the academic requirements for the degree of Master of Science at the University of Stellenbosch Supervisor: Dr Nyabadza Farai (University of Stellenbosch) December 2011 Stellenbosch University http://scholar.sun.ac.za Declaration By submitting this thesis/dissertation electronically, I declare that the entirety of the work contained therein is my own, original work, that I am the sole author thereof (save to the extent explicitly otherwise stated), that reproduction and publication thereof by Stellen- bosch University will not infringe any third party rights and that I have not previously in its entirety or in part submitted it for obtaining any qualification. November 21, 2011 - ---------------------------- ----------------------- Hatson John Boscoh Njagarah Date Copyright © 2011 Stellenbosch University All rights reserved. Stellenbosch University http://scholar.sun.ac.za i Abstract Substance abuse is an imminent danger on the health of both substance users and non- users. In general, abuse of psychoactive substances is associated with high risk behaviour, mortality and morbidity. The drug use cycle involves inextricably intertwined variants such as production, trading and usage of both licit and illicit addictive substances. The dynamics of substance use involve initiation, addiction, rehabilitation/treatment and quit- ting/recovery. In response to supply and abuse of monster drugs, control strategies such as law enforcement and rehabilitation have been stepped up to reduce access to drugs by targeting drug kingpins and harm reduction respectively. In this thesis, we model the fac- tors affecting the prevalence of substance abuse, the effect of drug lords on the prevalence of substance abuse, and the impact of substance abuse on the prevalence of HIV/AIDS.
    [Show full text]
  • HIV and Human Coronavirus Coinfections: a Historical Perspective
    viruses Review HIV and Human Coronavirus Coinfections: A Historical Perspective Palesa Makoti and Burtram C. Fielding * Molecular Biology and Virology Research Laboratory, Department of Medical Biosciences, University of the Western Cape, Cape Town 7535, South Africa; [email protected] * Correspondence: bfi[email protected]; Tel.: +27-21-959-2949 Received: 21 May 2020; Accepted: 2 August 2020; Published: 26 August 2020 Abstract: Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for HIV and hCoVs. Moreover, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases. Keywords: coronaviruses; HIV; COVID-19; SARS-CoV-2; MERS-CoV; immunosuppression; immune response; coinfection 1. Introduction With the rapid advancement of molecular diagnostic tools, our understanding of the etiological agents of respiratory tract infections (RTIs) has advanced rapidly [1]. Researchers now know that lower respiratory tract infections (LRTIs)—caused by viruses—are not restricted to the usual suspects, such as respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), adenovirus, human rhinoviruses (HRVs) and influenza viruses.
    [Show full text]
  • HIV/AIDS Programme Strengthening Health Services to Fight HIV/AIDS
    HIV/AIDS Programme Strengthening health services to fight HIV/AIDS ESSENTIAL PREVENTION AND CARE INTERVENTIONS FOR ADULTS AND ADOLESCENTS LIVING WITH HIV IN RESOURCE-LIMITED SETTINGS WHO Library Cataloguing-in-Publication Data Essential prevention and care interventions for adults and adolescents living with HIV in resource-limited settings / coordinated by Kevin O’Reilly. 1.HIV infections - prevention and control. 2.HIV infections - therapy. 3.HIV infections - complications. 4.Developing countries. I.World Health Organization. II.Boothroyd, Jim. ISBN 978 92 4 159670 1 (NLM classification: WC 503.5) © World Health Organization 2008 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • HIV/AIDS Guidelines
    Reproductive Options for Couples When One or Both Partners are Living with HIV (Last updated December 24, 2019; last reviewed December 24, 2019) Panel’s Recommendations For Couples Who Want to Conceive When One or Both Partners are Living with HIV: • Expert consultation is recommended to tailor guidance to couples’ specific needs (AIII). • Both partners should be screened and treated for genital tract infections before attempting to conceive (AII). • Partners with HIV should achieve sustained viral suppression (e.g., two recorded measurements of plasma viral loads that are below the limits of detection at least 3 months apart) before attempting conception to maximize their health, prevent HIV sexual transmission (AI) and, for pregnant persons with HIV, to minimize the risk of HIV transmission to the infant (AI). • For couples with differing HIV statuses, sexual intercourse without a condom allows for conception with effectively no risk of sexual HIV transmission to the partner without HIV when the partner with HIV is on antiretroviral therapy (ART) and has achieved sustained viral suppression (BII). • Additional guidance may be required in the following scenarios: • The partner with HIV has not achieved sustained viral suppression or the partner’s HIV viral suppression status is unknown, • There are concerns that the partner with HIV may be inconsistently adherent to ART during the periconception period, or • The provider needs to share additional information with the patient regarding options to prevent sexual HIV transmission during the periconception period. • In these circumstances, providers may choose to counsel their patient about the following options: • Administration of antiretroviral pre-exposure prophylaxis (PrEP) to the partner without HIV is recommended to reduce the risk of sexual acquisition of HIV (AI).
    [Show full text]
  • Reproductive Options for Couples When One Or Both Partners Have
    Reproductive Options for Couples When One or Both Partners Have HIV (Last updated December 29, 2020; last reviewed December 29, 2020) Panel’s Recommendations For Couples Who Want to Conceive When One or Both Partners Have HIV: • Expert consultation is recommended to tailor guidance to couples’ specific needs (AIII). • Both partners should be screened and treated for genital tract infections before attempting to conceive (AII). • Partners with HIV should achieve sustained viral suppression (e.g., two recorded measurements of plasma viral loads that are below the limits of detection at least 3 months apart) before attempting conception to maximize their health, prevent HIV sexual transmission (AI) and, for pregnant persons with HIV, to minimize the risk of HIV transmission to the infant (AI). • When partners have different HIV statuses, sexual intercourse without a condom allows conception with effectively no risk of sexual HIV transmission to the partner without HIV if the partner with HIV is on antiretroviral therapy (ART) and has achieved sustained viral suppression (BII). • Additional guidance might be required in the following scenarios: • The partner with HIV has not achieved sustained viral suppression or the partner’s HIV viral suppression status is unknown, • There are concerns that the partner with HIV might be inconsistently adherent to ART during the periconception period, or • The provider wishes to share additional information with the patient regarding options to prevent sexual HIV transmission during the periconception period. • In these circumstances, providers can choose to counsel their patient about the following options: • Administration of antiretroviral pre-exposure prophylaxis (PrEP) to the partner without HIV reduces the risk of sexual acquisition of HIV (AI) see Pre-exposure Prophylaxis (PrEP) to Reduce the Risk of Acquiring HIV During Periconception, Antepartum, and Postpartum Periods.
    [Show full text]
  • Serosorting and Strategic Positioning
    TECHNICAL BULLETIN SERIES Serosorting and Strategic Positioning What is serosorting? prevention does not yet have a definitive answer.22, 26, 27 • According to a World Health Organization (WHO) Serosorting is defined as “a person choosing a sexual partner systematic review that included 3 studies on serosort- known to be of the same HIV serostatus, often to engage in ing among MSM, serosorting was associated with a unprotected sex, in order to reduce the risk of acquiring or 79% increase in HIV transmission when compared with transmitting HIV.”1 It is a sexual risk management approach consistent condom use.17, 28-30 Serosorting has also been that has been identified among many groups of gay men and associated with a 61% increase in sexually transmit- other men who have sex with men (MSM), mostly in higher- ted infection (STI) transmission when compared with income countries.2-22 consistent condom use.30 • When serosorting was compared to no condom use, serosorting was associated with a 53% reduction in What is strategic positioning? HIV transmission and 14% reduction in STI transmis- sion.30 While evidence suggests that consistent condom Strategic positioning, also known as sero-positioning, is the use is a more effective means of HIV prevention than act of choosing a different sexual position or practice depend- serosorting, it appears that serosorting may be a viable ing on the serostatus of one’s partner.23 Typically, a person harm reduction strategy for those unwilling or unable living with HIV chooses to take the receptive position (“bot- to use condoms. This strategy depends on high cover- tom”) during unprotected anal sex with a partner believed to age rates of HIV testing, frequent utilization of HIV be HIV-negative.
    [Show full text]
  • Characterising Neutralising Antibody Responses in Hepatitis C Virus
    $ ! E\ #" $WKHVLVVXEPLWWHGDVSDUWLDOIXOILOPHQW RIWKHUHTXLUHPHQWIRUWKHGHJUHHRI 'RFWRURI3KLORVRSK\ ! " ! 6FKRRORI0HGLFDO6FLHQFHV.LUE\,QVWLWXWH )DFXOW\RI0HGLFLQH 8QLYHUVLW\RI1HZ6RXWK:DOHV 'HFHPEHU &(($$&#!(- ‘I hereby declare that this submission is my own work and to the best of my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linguistic expression is acknowledged.’ Signed…………………………………… Date ………………………… C $%-&('(("#( ‘I hereby grant the University of New South Wales or its agents a non ?R=FOMCP? FC=?H=?NI;L=BCP?;H>NIG;E?;P;CF;<F?CH=FO>CHANIG?G<?LMI@NB?JO<FC= GSNB?MCMIL>CMM?LN;NCIHCHQBIF?ILJ;LNCHNB?3HCP?LMCNSFC<L;LC?MCH;FF@ILGM I@G?>C; HIQILB?L?;@N?LEHIQH ';=EHIQF?>A?NB;N'L?N;CH;FFCHN?FF?=NO;F JLIJ?LNSLCABNMQBC=BMO<MCMNCHGSNB?MCMIL>CMM?LN;NCIH MO=B;M=IJSLCABN;H> J;N?HNLCABNM MO<D?=NNI;JJFC=;<F?F;Q ';FMIL?N;CHNB?LCABNNIOM?;FFILJ;LN of my thesis or dissertation in future works (such as articles or books).’ ‘For any substantial portions of copyright material used in this thesis, written J?LGCMMCIH@ILOM?B;M<??HI<N;CH?> ILNB?=IJSLCABNG;N?LC;FCML?GIP?>@LIG
    [Show full text]
  • Variable Effect of HIV Superinfection on Clinical Status: Insights from Mathematical Modeling
    ORIGINAL RESEARCH published: 23 July 2018 doi: 10.3389/fmicb.2018.01634 Variable Effect of HIV Superinfection on Clinical Status: Insights From Mathematical Modeling Ágnes Móréh 1, András Szilágyi 2,3, István Scheuring 2,3 and Viktor Müller 2,4* 1 MTA Centre for Ecological Research, Danube Research Institute, Budapest, Hungary, 2 Evolutionary Systems Research Group, MTA Centre for Ecological Research, Tihany, Hungary, 3 MTA-ELTE Theoretical Biology and Evolutionary Ecology Research Group, Institute of Biology, Eötvös Loránd University, Budapest, Hungary, 4 Department of Plant Systematics, Ecology and Theoretical Biology, Institute of Biology, Eötvös Loránd University, Budapest, Hungary HIV superinfection (infection of an HIV positive individual with another strain of the virus) has been shown to result in a deterioration of clinical status in multiple case studies. However, superinfection with no (or positive) clinical outcome might easily go unnoticed, and the typical effect of superinfection is unknown. We analyzed mathematical models of HIV dynamics to assess the effect of superinfection under various assumptions. We extended the basic model of virus dynamics to explore systematically a set of model variants incorporating various details of HIV infection (homeostatic target cell dynamics, bystander killing, interference competition between viral clones, multiple target cell types, virus-induced activation of target cells). In each model, we identified the conditions for Edited by: Esteban A. Hernandez-Vargas, superinfection, and investigated whether and how successful invasion by a second viral Frankfurt Institute for Advanced strain affects the level of uninfected target cells. In the basic model, and in some of Studies, Germany its extensions, the criteria for invasion necessarily entail a decrease in the equilibrium Reviewed by: abundance of uninfected target cells.
    [Show full text]