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Xinzhi Ren, Yanni Tian, Lili Liu, Xianning Liu
In this paper, a reaction-diffusion within-host HIV model is proposed. It incorporates cell mobility, spatial heterogeneity and cell-to-cell transmission, which depends on the diffusion ability of the infected cells. In the case of a bounded domain, the basic reproduction number [Formula: see text] is established and shown as a threshold: the virus-free steady state is globally asymptotically stable if [Formula: see text] and the virus is uniformly persistent if [Formula: see text]. The explicit formula for [Formula: see text] and the global asymptotic stability of the constant positive steady state are obtained for the case of homogeneous space...
January 5, 2018: Journal of Mathematical Biology
Rui Xu, Xiaohong Tian, Shihua Zhang
In this paper, a within-host HIV-1 infection model with virus-to-cell and direct cell-to-cell transmission and explicit age-since-infection structure for infected cells is investigated. It is shown that the model demonstrates a global threshold dynamics, fully described by the basic reproduction number. By analysing the corresponding characteristic equations, the local stability of an infection-free steady state and a chronic-infection steady state of the model is established. By using the persistence theory in infinite dimensional system, the uniform persistence of the system is established when the basic reproduction number is greater than unity...
December 2018: Journal of Biological Dynamics
Allan C deCamp, Morgane Rolland, Paul T Edlefsen, Eric Sanders-Buell, Breana Hall, Craig A Magaret, Andrew J Fiore-Gartland, Michal Juraska, Lindsay N Carpp, Shelly T Karuna, Meera Bose, Steven LePore, Shana Miller, Annemarie O'Sullivan, Kultida Poltavee, Hongjun Bai, Kalpana Dommaraju, Hong Zhao, Kim Wong, Lennie Chen, Hasan Ahmed, Derrick Goodman, Matthew Z Tay, Raphael Gottardo, Richard A Koup, Robert Bailer, John R Mascola, Barney S Graham, Mario Roederer, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Elizabeth Adams, Patricia D'Souza, James Kublin, Lawrence Corey, Daniel E Geraghty, Nicole Frahm, Georgia D Tomaras, M Juliana McElrath, Lisa Frenkel, Sheila Styrchak, Sodsai Tovanabutra, Magdalena E Sobieszczyk, Scott M Hammer, Jerome H Kim, James I Mullins, Peter B Gilbert
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120)...
2017: PloS One
Nargesalsadat Dorratoltaj, Ryan Nikin-Beers, Stanca M Ciupe, Stephen G Eubank, Kaja M Abbas
OBJECTIVE: The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level. BACKGROUND: While within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models is an emerging method to infer the synergistic dynamics of HIV at the individual and population levels...
2017: PeerJ
Suwellen S D de Azevedo, Diogo Gama Caetano, Fernanda H Côrtes, Sylvia L M Teixeira, Karina Dos Santos Silva, Brenda Hoagland, Beatriz Grinsztejn, Valdilea G Veloso, Mariza G Morgado, Gonzalo Bello
BACKGROUND: Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir's reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51-400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80-2000 copies/mL) viremia (VC, n = 10)...
May 2, 2017: Retrovirology
Michelle Zanoni, Ítalo Karmann Aventurato, James Hunter, Maria Cecilia Araripe Sucupira, Ricardo Sobhie Diaz
The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals...
2017: PloS One
Guy Baele, Marc A Suchard, Filip Bielejec, Philippe Lemey
Phylodynamic reconstructions rely on a measurable molecular footprint of epidemic processes in pathogen genomes. Identifying the factors that govern the tempo and mode by which these processes leave a footprint in pathogen genomes represents an important goal towards understanding infectious disease evolution. Discriminating between synonymous and non-synonymous substitution rates is crucial for testing hypotheses about the sources of evolutionary rate variation. Here, we implement a codon substitution model in a Bayesian statistical framework to estimate absolute rates of synonymous and non-synonymous substitution in unknown evolutionary histories...
June 2016: Microbial Genomics
Cameron Browne
Mathematical modeling and analysis can provide insight on the dynamics of ecosystems which maintain biodiversity in the face of competitive and prey-predator interactions. Of primary interests are the underlying structure and features which stabilize diverse ecological networks. Recently Korytowski and Smith (Theor Ecol 8(1):111-120, 2015) proved that a perfectly nested infection network, along with appropriate life history trade-offs, leads to coexistence and persistence of bacteria-phage communities in a chemostat model...
October 2017: Journal of Mathematical Biology
Israel Pagán, Patricia Rojas, José Tomás Ramos, África Holguín
Understanding the factors that modulate the evolution of virus populations is essential to design efficient control strategies. Mathematical models predict that factors affecting viral within-host evolution may also determine that at the between-host level. Although HIV-1 within-host evolution has been associated with clinical factors used to monitor AIDS progression, such as patient age, CD4 cells count, viral load, and antiretroviral experience, little is known about the role of these clinical factors in determining between-host HIV-1 evolution...
2016: PloS One
Vlad Novitsky, Sikhulile Moyo, Rui Wang, Simani Gaseitsiwe, M Essex
BACKGROUND: A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies. METHODOLOGY: We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources...
2016: PloS One
Filip Bielejec, Guy Baele, Allen G Rodrigo, Marc A Suchard, Philippe Lemey
Various factors determine the rate at which mutations are generated and fixed in viral genomes. Viral evolutionary rates may vary over the course of a single persistent infection and can reflect changes in replication rates and selective dynamics. Dedicated statistical inference approaches are required to understand how the complex interplay of these processes shapes the genetic diversity and divergence in viral populations. Although evolutionary models accommodating a high degree of complexity can now be formalized, adequately informing these models by potentially sparse data, and assessing the association of the resulting estimates with external predictors, remains a major challenge...
July 2016: Virus Evolution
Walter Chingwaru, Richard H Glashoff, Jerneja Vidmar, Petrina Kapewangolo, Samantha L Sampson
Mycobacterium tuberculosis and human immunodeficiency virus (HIV) co-infections have remained a major public health concern worldwide, particularly in Southern Africa. Yet our understanding of the molecular interactions between the pathogens has remained poor due to lack of suitable preclinical models for such studies. We reviewed the use, this far, of mammalian cell culture models in HIV-MTB interaction studies. Studies have described the use of primary human cell cultures, including (1) monocyte-derived macrophage (MDM) fractions of peripheral blood mononuclear cell (PBMC), alveolar macrophages (AM), (2) cell lines such as the monocyte-derived macrophage cell line (U937), T lymphocyte cell lines (CEMx174, ESAT-6-specific CD4(+) T-cells) and an alveolar epithelial cell line (A549) and (3) special models such as stem cells, three dimensional (3D) or organoid cell models (including a blood-brain barrier cell model) in HIV-MTB interaction studies...
September 2016: Asian Pacific Journal of Tropical Medicine
John P Barton, Nilu Goonetilleke, Thomas C Butler, Bruce D Walker, Andrew J McMichael, Arup K Chakraborty
Human immunodeficiency virus (HIV) evolves within infected persons to escape being destroyed by the host immune system, thereby preventing effective immune control of infection. Here, we combine methods from evolutionary dynamics and statistical physics to simulate in vivo HIV sequence evolution, predicting the relative rate of escape and the location of escape mutations in response to T-cell-mediated immune pressure in a cohort of 17 persons with acute HIV infection. Predicted and clinically observed times to escape immune responses agree well, and we show that the mutational pathways to escape depend on the viral sequence background due to epistatic interactions...
May 23, 2016: Nature Communications
Himanshu Garg, Raphael T C Lee, Sebastian Maurer-Stroh, Anjali Joshi
Variability in CCR5 levels in the human population is suggested to affect virus evolution, fitness and the course of HIV disease. We previously demonstrated that cell surface CCR5 levels directly affect HIV Envelope mediated bystander apoptosis. In this study, we attempted to understand HIV evolution in the presence of low levels of CCR5, mimicking the limiting CCR5 levels inherent to the host. HIV-1 adaptation in a T cell line expressing low levels of CCR5 resulted in two specific mutations; N302Y and E172K...
June 2016: Virology
José Miguel Azevedo-Pereira, Quirina Santos-Costa
HIV-1 and HIV-2 are the causal agents of AIDS. While similar in many ways, a significant amount of data suggests that HIV-2 is less virulent than HIV-1. In fact, HIV-2 infection is characterized by a longer asymptomatic stage and lower transmission rate, and the majority of HIV-2-infected patients can be classified as long-term non-progressors or elite controllers. The mechanisms underlying the ability of human host to naturally control HIV-2 infection are far from being completely understood. The identification of the differences between HIV-1 and HIV-2 interactions with human host cells could provide important insights into several aspects of retroviral pathogenesis that remain elusive, with significant implications for HIV vaccine development and therapy...
January 2016: AIDS Reviews
Kevin Dialdestoro, Jonas Andreas Sibbesen, Lasse Maretty, Jayna Raghwani, Astrid Gall, Paul Kellam, Oliver G Pybus, Jotun Hein, Paul A Jenkins
Human immunodeficiency virus (HIV) is a rapidly evolving pathogen that causes chronic infections, so genetic diversity within a single infection can be very high. High-throughput "deep" sequencing can now measure this diversity in unprecedented detail, particularly since it can be performed at different time points during an infection, and this offers a potentially powerful way to infer the evolutionary dynamics of the intrahost viral population. However, population genomic inference from HIV sequence data is challenging because of high rates of mutation and recombination, rapid demographic changes, and ongoing selective pressures...
April 2016: Genetics
Etai Rotem, Eliran Moshe Reuven, Yoel A Klug, Yechiel Shai
To successfully infect and persist within its host, HIV-1 utilizes several immunosuppressive motifs within its gp41 envelope glycoprotein to manipulate and evade the immune system. The transmembrane domain (TMD) of gp41 downregulates T-cell receptor (TCR) signaling through a hitherto unknown mechanism. Interactions between TMDs within the membrane milieu have been shown to be typically mediated by particular amino acids, such as interactions between basic and acidic residues and dimerization motifs as GxxxG...
February 23, 2016: Biochemistry
Anh Q Le, Jeremy Taylor, Winnie Dong, Rosemary McCloskey, Conan Woods, Ryan Danroth, Kanna Hayashi, M-J Milloy, Art F Y Poon, Zabrina L Brumme
Rare individuals homozygous for a naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5∆32/∆32) are resistant to infection by CCR5-using ("R5") HIV-1 strains but remain susceptible to less common CXCR4-using ("X4") strains. The evolutionary dynamics of X4 infections however, remain incompletely understood. We identified two individuals, one CCR5wt/wt and one CCR5∆32/∆32, within the Vancouver Injection Drug Users Study who were infected with a genetically similar X4 HIV-1 strain. While early-stage plasma viral loads were comparable in the two individuals (~4...
December 3, 2015: Scientific Reports
Alexander O Pasternak, Laura K DeMaster, Neeltje A Kootstra, Peter Reiss, Una O'Doherty, Ben Berkhout
Cell-associated HIV unspliced RNA is an important marker of the viral reservoir. HIV gag RNA-specific assays are frequently used to monitor reservoir activation. Because HIV preferentially integrates into actively transcribed genes, some of the transcripts detected by these assays may not represent genuine HIV RNA but rather chimeric host-HIV readthrough transcripts. Here, we demonstrate that in HIV-infected patients on suppressive combination antiretroviral therapy, such host-derived transcripts do not significantly contribute to the HIV gag RNA level...
January 15, 2016: Journal of Virology
Jagganatha Rao Ravi, Tuthipat Ramachandra Gururaja Rao
INTRODUCTION: Acquired Immuno Deficiency Syndrome (AIDS) is a condition in which the body becomes susceptible to a host of opportunistic infections. This syndrome is a culmination of infection with a lenti virus called Human Immunodeficiency Virus (HIV) particularly HIV 1. A cross section of the population including adults and children are affected by HIV infection with estimate of 36.1 million affected by the end of 2014. HIV infection affects the T lymphocytes especially cluster of differentiation 4 (CD4) count reducing it drastically jeopardizing the acquired immunity...
July 2015: Journal of Indian Society of Periodontology
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