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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...
February 20, 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 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
Íris M Santos, Elis A da Rosa, Tiago Gräf, Luiz G E Ferreira, Andrea Petry, Fernanda Cavalheiro, Edna M Reiche, Carlos R Zanetti, Aguinaldo R Pinto
Individuals who have been exposed to human immunodeficiency virus (HIV) and have not been infected might possess natural resistance mechanisms. An understanding of the sociodemographic and immunological conditions that influence resistance to HIV is a challenge, and very little is known about the role of intrinsic antiviral factors that restrict HIV infection. The aim of this study was to analyze potential factors responsible for resistance to HIV infection in serodiscordant couples by comparing HIV-exposed seronegative individuals (HESN) to HIV-seropositive individuals treated with antiretroviral therapy (HIV-ART) along with healthy controls (HC)...
November 2015: AIDS Research and Human Retroviruses
Kyaw Linn, Alexander Fay, Katherine Meddles, Sara Isbell, Phyo Nay Lin, Cho Thair, Jodi Heaps, Robert Paul, Soe Soe Mar
OBJECTIVE: We determined the effect of perinatally acquired HIV on neurocognition in Myanmar children treated with antiretroviral therapy by comparison to demographically matched seronegative children. BACKGROUND: Myanmar has one of the highest HIV-1 prevalence rates in Southeast Asia. Studies from other resource-poor countries have shown that HIV-infected children differ in socioeconomic, nutritional and caregiver status compared to normal controls. Some vertically infected orphans in Myanmar reside separately from HIV-uninfected children in separate orphanages, thus the demographic variables of interest are naturally controlled...
December 2015: Pediatric Neurology
Gajendra W Suryawanshi, Alexander Hoffmann
Human immunodeficiency virus-1 (HIV-1) employs accessory proteins to evade innate immune responses by neutralizing the anti-viral activity of host restriction factors. Apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, A3G) and bone marrow stromal cell antigen 2 (BST2) are host resistance factors that potentially inhibit HIV-1 infection. BST2 reduces viral production by tethering budding HIV-1 particles to virus producing cells, while A3G inhibits the reverse transcription (RT) process and induces viral genome hypermutation through cytidine deamination, generating fewer replication competent progeny virus...
December 7, 2015: Journal of Theoretical Biology
Wenjiao Wu, Dongguo Lin, Xintian Shen, Fangfang Li, Yuxin Fang, Kaiqun Li, Tianrong Xun, Guang Yang, Jie Yang, Shuwen Liu, Jian He
Influenza A viral (IAV) fusion peptides are known for their important role in viral-cell fusion process and membrane destabilization potential which are compatible with those of antimicrobial peptides. Thus, by replacing the negatively or neutrally charged residues of FPs with positively charged lysines, we synthesized several potent antimicrobial peptides derived from the fusogenic peptides (FPs) of hemagglutinin glycoproteins (HAs) of IAV. The biological screening identified that in addition to the potent antibacterial activities, these positively charged fusion peptides (pFPs) effectively inhibited the replication of influenza A viruses including oseltamivir-resistant strain...
2015: PloS One
Zhengyu Ouyang, Maria J Buzon, Lu Zheng, Hong Sun, Xu G Yu, Ronald J Bosch, John W Mellors, Joseph J Eron, Rajesh T Gandhi, Mathias Lichterfeld
Background.  Intensification of antiretroviral therapy with raltegravir does not affect levels of residual human immunodeficiency virus (HIV)-1 viremia, but it has led to increased levels of episomal HIV-1 DNA in some patients, suggesting antiviral activity against otherwise unresponsive components of the viral reservoir. Effects of raltegravir on host cells remain less well understood. Methods.  We used comprehensive and unbiased microarray-based transcriptional profiling to analyze gene expression changes in CD8(+) T cells from participants in a randomized clinical trial (AIDS Clinical Trials Group [ACTG] A5244) comparing raltegravir-intensified to nonintensified antiretroviral therapy...
April 2015: Open Forum Infectious Diseases
Feng Huang, Junsong Zhang, Yijun Zhang, Guannan Geng, Juanran Liang, Yingniang Li, Jingliang Chen, Chao Liu, Hui Zhang
Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis...
December 2015: Virology
Katarzyna Kaczmarek Michaels, Frank Wolschendorf, Gillian M Schiralli Lester, Malini Natarajan, Olaf Kutsch, Andrew J Henderson
Since HIV-1 has a propensity to integrate into actively expressed genes, transcriptional interference from neighboring host promoters has been proposed to contribute to the establishment and maintenance HIV-1 latency. To gain insights into how endogenous promoters influence HIV-1 transcription we utilized a set of inducible T cell lines and characterized whether there were correlations between expression of endogenous genes, provirus and long terminal repeat architecture. We show that neighboring promoters are active but have minimal impact on HIV-1 transcription, in particular, expression of the endogenous gene did not prevent expression of HIV-1 following induction of latent provirus...
December 2015: Virology
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