Special Issue "HIV Dynamics and Evolution"
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A special issue of Viruses (ISSN 1999-4915).
Deadline for manuscript submissions: closed (31 October 2012)
Special Issue Editor
Guest Editor
Dr. Viktor Müller
Institute of Biology, Eötvös Loránd University, Pázmány P. s. 1/C, 1117 Budapest, Hungary
Website: http://ramet.elte.hu/~viktor/
E-Mail: muller_v@ludens.elte.hu
Phone: +36 1 372 2500/8798
Fax: +36 1 381 2188
Interests: virus dynamics; HIV evolution and epidemiology
Special Issue Information
Dear Colleagues,
HIV is the youngest of the major human pathogens, yet it has become the leading infectious cause of death worldwide. Thirty years of intensive research have revealed a highly complex disease dynamics, calling for quantitative approaches to interpret the experimental data and to aid the understanding of the underlying processes that govern the dynamics and progression of the disease. This Special Issue of Viruses is open to both empirical and mathematical/modelling papers addressing HIV/SIV dynamics in a broad sense (including within-host, cellular and population level dynamics).
The second focus topic is the evolution of HIV: its origins and historical evolution, its current evolution within the host and at the population level, co-evolution of virus and host, molecular evolution and the evolution of phenotypic traits (e.g. virulence, replication capacity or drug resistance). The Special Issue is open to both phylogenetic and bioinformatics analyses, and to theoretical/modelling approaches to the evolution of HIV and SIV viruses.
Dr. Viktor Müller
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1200 CHF (Swiss Francs).
Keywords
- HIV/SIV
- virus dynamics
- mathematical/simulation modelling
- virus evolution
- phylogenetics
- phylodynamics
- data analysis
Published Papers (7 papers)
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Received: 5 February 2012; in revised form: 29 February 2012 / Accepted: 1 March 2012 / Published: 5 March 2012
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Abstract: The Protein Data Bank (PDB) contains over 71,000 structures. Extensively studied proteins have hundreds of submissions available, including mutations, different complexes, and space groups, allowing for application of data-mining algorithms to analyze an array of static structures and gain insight about a protein’s structural variation and possibly its dynamics. This investigation is a case study of HIV protease (PR) using in-house algorithms for data mining and structure superposition through generalized formulæ that account for multiple conformations and fractional occupancies. Temperature factors (B-factors) are compared with spatial displacement from the mean structure over the entire study set and separately over bound and ligand-free structures, to assess the significance of structural deviation in a statistical context. Space group differences are also examined.
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Received: 11 July 2012; in revised form: 3 August 2012 / Accepted: 6 August 2012 / Published: 7 August 2012
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Abstract: When HIV-1 is exposed to lamivudine (3TC) at inhibitory concentrations, resistant variants carrying the reverse transcriptase (RT) substitution M184V emerge rapidly. This substitution confers high-level 3TC resistance and increased RT fidelity. We established a novel in vitro system to study the effect of starting nevirapine (NVP) in 3TC-resistant/NNRTI-naïve clinical isolates, and the impact of maintaining versus dropping 3TC pressure in this setting. Because M184V mutant HIV-1 seems hypersusceptible to adefovir (ADV), we also tested the effect of ADV pressure on the same isolates. We draw four conclusions from our experiments simulating combination therapy in vitro. (1) The presence of low-dose (1 μM) 3TC prevented reversal to wild-type from an M184V mutant background. (2) Adding low-dose 3TC in the presence of NVP delayed the selection of NVP-associated mutations. (3) The presence of ADV, in addition to NVP, led to more rapid reversal to wild-type at position 184 than NVP alone. (4) ADV plus NVP selected for greater numbers of mutations than NVP alone. Inference about the “selection of mutation” is based on two statistical models, one at the viral level, more telling, and the other at the level of predominance of mutation within a population. Multidrug pressure experiments lend understanding to mechanisms of HIV resistance as they bear upon new treatment strategies.
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Graeme B. Jacobs, Stefanie Bock, Anita Schuch, Rebecca Moschall, Eva-Maria Schrom, Juliane Zahn, Christian Reuter, Wolfgang Preiser, Axel Rethwilm, Susan Engelbrecht, Thomas Kerkau and Jochen Bodem
Received: 26 July 2012; in revised form: 13 September 2012 / Accepted: 13 September 2012 / Published: 24 September 2012
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Abstract: The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317.
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Received: 6 September 2012; in revised form: 15 September 2012 / Accepted: 17 September 2012 / Published: 3 October 2012
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Abstract: HIV-1 M originated from SIVcpz endemic in chimpanzees from southeast Cameroon or neighboring areas, and it started to spread in the early 20th century. Here we examine the factors that may have contributed to simian-to-human transmission, local transmission between humans, and export to a city. The region had intense ape hunting, social disruption, commercial sex work, STDs, and traffic to/from Kinshasa in the period 1899–1923. Injection treatments increased sharply around 1930; however, their frequency among local patients was far lower than among modern groups experiencing parenteral HIV-1 outbreaks. Recent molecular datings of HIV-1 M fit better the period of maximal resource exploitation and trade links than the period of high injection intensity. We conclude that although local parenteral outbreaks might have occurred, these are unlikely to have caused massive transmission. World War I led to additional, and hitherto unrecognized, risks of HIV-1 emergence. We propose an Enhanced Heterosexual Transmission Hypothesis for the origin of HIV-1 M, featuring at the time and place of its origin a coincidence of favorable co-factors (ape hunting, social disruption, STDs, and mobility) for both cross-species transmission and heterosexual spread. Our hypothesis does not exclude a role for parenteral transmission in the initial viral adaptation.
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Received: 28 August 2012; in revised form: 19 September 2012 / Accepted: 28 September 2012 / Published: 4 October 2012
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Abstract: The Human Immunodeficiency Virus (HIV) is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells). However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection.
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Received: 2 August 2012; in revised form: 18 September 2012 / Accepted: 7 October 2012 / Published: 10 October 2012
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Abstract: The dynamics of HIV–1 viremia is a complex and evolving landscape with clinical and epidemiological (public health) implications. Most studies have relied on the use of set–point viral load (VL) as a readily available proxy of viral dynamics to assess host and viral correlates. This review highlights recent findings from population–based studies of set–point VL, focusing primarily on robust data related to host genetics. A comprehensive understanding of viral dynamics will clearly need to consider both host and viral characteristics, with close attention to (i) the timing of VL measurements, (ii) the biology of viral evolution, (iii) compartments of active viral replication, (iv) the transmission source partner as the immediate past microenvironment, and (v) proper application of statistical models.
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Received: 25 September 2012; in revised form: 29 October 2012 / Accepted: 5 November 2012 / Published: 14 November 2012
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Abstract: Human immunodeficiency virus-1 (HIV-1) dynamics reflect an intricate balance within the viruses’ host. The virus relies on host replication factors, but must escape or counter its host’s antiviral restriction factors. The interaction between the HIV-1 protein Vif and many cellular restriction factors from the APOBEC3 protein family is a prominent example of this evolutionary arms race. The viral infectivity factor (Vif) protein largely neutralizes APOBEC3 proteins, which can induce in vivo hypermutations in HIV-1 to the extent of lethal mutagenesis, and ensures the production of viable virus particles. HIV-1 also uses the APOBEC3-Vif interaction to modulate its own mutation rate in harsh or variable environments, and it is a model of adaptation in a coevolutionary setting. Both experimental evidence and the substantiation of the underlying dynamics through coevolutionary models are presented as complementary views of a coevolutionary arms race.
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Last update: 28 January 2013
