Biology

203 KiB

Open AccessReview

Why Assembling Plant Genome Sequences Is So Challenging

by Manuel Gonzalo Claros, Rocío Bautista, Darío Guerrero-Fernández, Hicham Benzerki, Pedro Seoane and Noé Fernández-Pozo

Biology 2012, 1(2), 439-459; https://doi.org/10.3390/biology1020439 - 18 Sep 2012

Cited by 96 | Viewed by 13916

Abstract

In spite of the biological and economic importance of plants, relatively few plant species have been sequenced. Only the genome sequence of plants with relatively small genomes, most of them angiosperms, in particular eudicots, has been determined. The arrival of next-generation sequencing technologies [...] Read more.

In spite of the biological and economic importance of plants, relatively few plant species have been sequenced. Only the genome sequence of plants with relatively small genomes, most of them angiosperms, in particular eudicots, has been determined. The arrival of next-generation sequencing technologies has allowed the rapid and efficient development of new genomic resources for non-model or orphan plant species. But the sequencing pace of plants is far from that of animals and microorganisms. This review focuses on the typical challenges of plant genomes that can explain why plant genomics is less developed than animal genomics. Explanations about the impact of some confounding factors emerging from the nature of plant genomes are given. As a result of these challenges and confounding factors, the correct assembly and annotation of plant genomes is hindered, genome drafts are produced, and advances in plant genomics are delayed. Full article

(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)

251 KiB

Open AccessReview

Investigating Climate Change and Reproduction: Experimental Tools from Evolutionary Biology

by Vera M. Grazer and Oliver Y. Martin

Biology 2012, 1(2), 411-438; https://doi.org/10.3390/biology1020411 - 13 Sep 2012

Cited by 24 | Viewed by 8280

Abstract

It is now generally acknowledged that climate change has wide-ranging biological consequences, potentially leading to impacts on biodiversity. Environmental factors can have diverse and often strong effects on reproduction, with obvious ramifications for population fitness. Nevertheless, reproductive traits are often neglected in conservation [...] Read more.

It is now generally acknowledged that climate change has wide-ranging biological consequences, potentially leading to impacts on biodiversity. Environmental factors can have diverse and often strong effects on reproduction, with obvious ramifications for population fitness. Nevertheless, reproductive traits are often neglected in conservation considerations. Focusing on animals, recent progress in sexual selection and sexual conflict research suggests that reproductive costs may pose an underestimated hurdle during rapid climate change, potentially lowering adaptive potential and increasing extinction risk of certain populations. Nevertheless, regime shifts may have both negative and positive effects on reproduction, so it is important to acquire detailed experimental data. We hence present an overview of the literature reporting short-term reproductive consequences of exposure to different environmental factors. From the enormous diversity of findings, we conclude that climate change research could benefit greatly from more coordinated efforts incorporating evolutionary approaches in order to obtain cross-comparable data on how individual and population reproductive fitness respond in the long term. Therefore, we propose ideas and methods concerning future efforts dealing with reproductive consequences of climate change, in particular by highlighting the advantages of multi-generational experimental evolution experiments. Full article

(This article belongs to the Special Issue Biological Implications of Climate Change)

936 KiB

Open AccessArticle

TE-Locate: A Tool to Locate and Group Transposable Element Occurrences Using Paired-End Next-Generation Sequencing Data

by Alexander Platzer, Viktoria Nizhynska and Quan Long

Biology 2012, 1(2), 395-410; https://doi.org/10.3390/biology1020395 - 12 Sep 2012

Cited by 30 | Viewed by 10456

Abstract

Transposable elements (TEs) are common mobile DNA elements present in nearly all genomes. Since the movement of TEs within a genome can sometimes have phenotypic consequences, an accurate report of TE actions is desirable. To this end, we developed TE-Locate, a computational tool [...] Read more.

Transposable elements (TEs) are common mobile DNA elements present in nearly all genomes. Since the movement of TEs within a genome can sometimes have phenotypic consequences, an accurate report of TE actions is desirable. To this end, we developed TE-Locate, a computational tool that uses paired-end reads to identify the novel locations of known TEs. TE-Locate can utilize either a database of TE sequences, or annotated TEs within the reference sequence of interest. This makes TE-Locate useful in the search for any mobile sequence, including retrotransposed gene copies. One major concern is to act on the correct hierarchy level, thereby avoiding an incorrect calling of a single insertion as multiple events of TEs with high sequence similarity. We used the (super)family level, but TE-Locate can also use any other level, right down to the individual transposable element. As an example of analysis with TE-Locate, we used the Swedish population in the 1,001 Arabidopsis genomes project, and presented the biological insights gained from the novel TEs, inducing the association between different TE superfamilies. The program is freely available, and the URL is provided in the end of the paper. Full article

(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)

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143 KiB

Open AccessReview

Next-Generation Sequencing: Application in Liver Cancer—Past, Present and Future?

by Jens U. Marquardt and Jesper B. Andersen

Biology 2012, 1(2), 383-394; https://doi.org/10.3390/biology1020383 - 31 Aug 2012

Cited by 13 | Viewed by 7362

Abstract

Hepatocellular Carcinoma (HCC) is the third most deadly malignancy worldwide characterized by phenotypic and molecular heterogeneity. In the past two decades, advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. More recently, improvements of sophisticated [...] Read more.

Hepatocellular Carcinoma (HCC) is the third most deadly malignancy worldwide characterized by phenotypic and molecular heterogeneity. In the past two decades, advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. More recently, improvements of sophisticated next-generation sequencing (NGS) technologies have enabled complete and cost-efficient analyses of cancer genomes at a single nucleotide resolution and advanced into valuable tools in translational medicine. Although the use of NGS in human liver cancer is still in its infancy, great promise rests in the systematic integration of different molecular analyses obtained by these methodologies, i.e., genomics, transcriptomics and epigenomics. This strategy is likely to be helpful in identifying relevant and recurrent pathophysiological hallmarks thereby elucidating our limited understanding of liver cancer. Beside tumor heterogeneity, progress in translational oncology is challenged by the amount of biological information and considerable “noise” in the data obtained from different NGS platforms. Nevertheless, the following review aims to provide an overview of the current status of next-generation approaches in liver cancer, and outline the prospects of these technologies in diagnosis, patient classification, and prediction of outcome. Further, the potential of NGS to identify novel applications for concept clinical trials and to accelerate the development of new cancer therapies will be summarized. Full article

(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)

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Open AccessArticle

Discovery of Single Nucleotide Polymorphisms in Complex Genomes Using SGSautoSNP

by Michał T. Lorenc, Satomi Hayashi, Jiri Stiller, Hong Lee, Sahana Manoli, Pradeep Ruperao, Paul Visendi, Paul J. Berkman, Kaitao Lai, Jacqueline Batley and David Edwards

Biology 2012, 1(2), 370-382; https://doi.org/10.3390/biology1020370 - 27 Aug 2012

Cited by 55 | Viewed by 10349

Abstract

Single nucleotide polymorphisms (SNPs) are becoming the dominant form of molecular marker for genetic and genomic analysis. The advances in second generation DNA sequencing provide opportunities to identify very large numbers of SNPs in a range of species. However, SNP identification remains a [...] Read more.

Single nucleotide polymorphisms (SNPs) are becoming the dominant form of molecular marker for genetic and genomic analysis. The advances in second generation DNA sequencing provide opportunities to identify very large numbers of SNPs in a range of species. However, SNP identification remains a challenge for large and polyploid genomes due to their size and complexity. We have developed a pipeline for the robust identification of SNPs in large and complex genomes using Illumina second generation DNA sequence data and demonstrated this by the discovery of SNPs in the hexaploid wheat genome. We have developed a SNP discovery pipeline called SGSautoSNP (Second-Generation Sequencing AutoSNP) and applied this to discover more than 800,000 SNPs between four hexaploid wheat cultivars across chromosomes 7A, 7B and 7D. All SNPs are presented for download and viewing within a public GBrowse database. Validation suggests an accuracy of greater than 93% of SNPs represent polymorphisms between wheat cultivars and hence are valuable for detailed diversity analysis, marker assisted selection and genotyping by sequencing. The pipeline produces output in GFF3, VCF, Flapjack or Illumina Infinium design format for further genotyping diverse populations. As well as providing an unprecedented resource for wheat diversity analysis, the method establishes a foundation for high resolution SNP discovery in other large and complex genomes. Full article

(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)

451 KiB

Open AccessReview

Transcriptional Gene Silencing (TGS) via the RNAi Machinery in HIV-1 Infections

by Gavin C. Sampey, Irene Guendel, Ravi Das, Elizabeth Jaworski, Zachary Klase, Aarthi Narayanan, Kylene Kehn-Hall and Fatah Kashanchi

Biology 2012, 1(2), 339-369; https://doi.org/10.3390/biology1020339 - 24 Aug 2012

Cited by 9 | Viewed by 12833

Abstract

Gene silencing via non-coding RNA, such as siRNA and miRNA, can occur at the transcriptional, post-transcriptional, and translational stages of expression. Transcriptional gene silencing (TGS) involving the RNAi machinery generally occurs through DNA methylation, as well as histone post-translational modifications, and corresponding remodeling [...] Read more.

Gene silencing via non-coding RNA, such as siRNA and miRNA, can occur at the transcriptional, post-transcriptional, and translational stages of expression. Transcriptional gene silencing (TGS) involving the RNAi machinery generally occurs through DNA methylation, as well as histone post-translational modifications, and corresponding remodeling of chromatin around the target gene into a heterochromatic state. The mechanism by which mammalian TGS occurs includes the recruitment of RNA-induced initiation of transcriptional gene silencing (RITS) complexes, DNA methyltransferases (DNMTs), and other chromatin remodelers. Additionally, virally infected cells encoding miRNAs have also been shown to manipulate the host cell RNAi machinery to induce TGS at the viral genome, thereby establishing latency. Furthermore, the introduction of exogenous siRNA and shRNA into infected cells that target integrated viral promoters can greatly suppress viral transcription via TGS. Here we examine the latest findings regarding mammalian TGS, specifically focusing on HIV-1 infected cells, and discuss future avenues of exploration in this field. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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848 KiB

Open AccessReview

Computer-Aided Approaches for Targeting HIVgp41

by William J. Allen and Robert C. Rizzo

Biology 2012, 1(2), 311-338; https://doi.org/10.3390/biology1020311 - 20 Aug 2012

Cited by 17 | Viewed by 9611

Abstract

Virus-cell fusion is the primary means by which the human immunodeficiency virus-1 (HIV) delivers its genetic material into the human T-cell host. Fusion is mediated in large part by the viral glycoprotein 41 (gp41) which advances through four distinct conformational states: (i [...] Read more.

Virus-cell fusion is the primary means by which the human immunodeficiency virus-1 (HIV) delivers its genetic material into the human T-cell host. Fusion is mediated in large part by the viral glycoprotein 41 (gp41) which advances through four distinct conformational states: (i) native, (ii) pre-hairpin intermediate, (iii) fusion active (fusogenic), and (iv) post-fusion. The pre-hairpin intermediate is a particularly attractive step for therapeutic intervention given that gp41 N-terminal heptad repeat (NHR) and C‑terminal heptad repeat (CHR) domains are transiently exposed prior to the formation of a six-helix bundle required for fusion. Most peptide-based inhibitors, including the FDA‑approved drug T20, target the intermediate and there are significant efforts to develop small molecule alternatives. Here, we review current approaches to studying interactions of inhibitors with gp41 with an emphasis on atomic-level computer modeling methods including molecular dynamics, free energy analysis, and docking. Atomistic modeling yields a unique level of structural and energetic detail, complementary to experimental approaches, which will be important for the design of improved next generation anti-HIV drugs. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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313 KiB

Open AccessReview

Analyzing the microRNA Transcriptome in Plants Using Deep Sequencing Data

by Xiaozeng Yang and Lei Li

Biology 2012, 1(2), 297-310; https://doi.org/10.3390/biology1020297 - 15 Aug 2012

Cited by 12 | Viewed by 10785

Abstract

MicroRNAs (miRNAs) are 20- to 24-nucleotide endogenous small RNA molecules emerging as an important class of sequence-specific, trans-acting regulators for modulating gene expression at the post-transcription level. There has been a surge of interest in the past decade in identifying miRNAs and [...] Read more.

MicroRNAs (miRNAs) are 20- to 24-nucleotide endogenous small RNA molecules emerging as an important class of sequence-specific, trans-acting regulators for modulating gene expression at the post-transcription level. There has been a surge of interest in the past decade in identifying miRNAs and profiling their expression pattern using various experimental approaches. In particular, ultra-deep sampling of specifically prepared low-molecular-weight RNA libraries based on next-generation sequencing technologies has been used successfully in diverse species. The challenge now is to effectively deconvolute the complex sequencing data to provide comprehensive and reliable information on the miRNAs, miRNA precursors, and expression profile of miRNA genes. Here we review the recently developed computational tools and their applications in profiling the miRNA transcriptomes, with an emphasis on the model plant Arabidopsis thaliana. Highlighted is also progress and insight into miRNA biology derived from analyzing available deep sequencing data. Full article

(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)

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873 KiB

Open AccessArticle

HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods

by Vo Cam Quy, Sergio Pantano, Giulia Rossetti, Mauro Giacca and Paolo Carloni

Biology 2012, 1(2), 277-296; https://doi.org/10.3390/biology1020277 - 13 Aug 2012

Cited by 8 | Viewed by 8823

Abstract

The binding between the HIV-1 trans-activator of transcription (Tat) and p300/(CREB-binding protein)-associated factor (PCAF) bromodomain is a crucial step in the HIV-1 life cycle. However, the structure of the full length acetylated Tat bound to PCAF has not been yet determined experimentally. [...] Read more.

The binding between the HIV-1 trans-activator of transcription (Tat) and p300/(CREB-binding protein)-associated factor (PCAF) bromodomain is a crucial step in the HIV-1 life cycle. However, the structure of the full length acetylated Tat bound to PCAF has not been yet determined experimentally. Acetylation of Tat residues can play a critical role in enhancing HIV-1 transcriptional activation. Here, we have combined a fully flexible protein-protein docking approach with molecular dynamics simulations to predict the structural determinants of the complex for the common HIV-1_BRU variant. This model reproduces all the crucial contacts between the Tat peptide ⁴⁶SYGR(AcK)KRRQRC⁵⁶ and the PCAF bromodomain previously reported by NMR spectroscopy. Additionally, inclusion of the entire Tat protein results in additional contact points at the protein-protein interface. The model is consistent with the available experimental data reported and adds novel information to our previous structural predictions of the PCAF bromodomain in complex with the rare HIV_Z2 variant, which was obtained with a less accurate computational method. This improved characterization of Tat.PCAF bromodomain binding may help in defining the structural determinants of other protein interactions involving lysine acetylation. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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1889 KiB

Open AccessArticle

A Comparison of Two Single-Stranded DNA Binding Models by Mutational Analysis of APOBEC3G

by Keisuke Shindo, Ming Li, Phillip J. Gross, William L. Brown, Elena Harjes, Yongjian Lu, Hiroshi Matsuo and Reuben S. Harris

Biology 2012, 1(2), 260-276; https://doi.org/10.3390/biology1020260 - 2 Aug 2012

Cited by 15 | Viewed by 7381

Abstract

APOBEC3G is the best known of several DNA cytosine deaminases that function to inhibit the replication of parasitic genetic elements including the lentivirus HIV. Several high-resolution structures of the APOBEC3G catalytic domain have been generated, but none reveal how this enzyme binds to [...] Read more.

APOBEC3G is the best known of several DNA cytosine deaminases that function to inhibit the replication of parasitic genetic elements including the lentivirus HIV. Several high-resolution structures of the APOBEC3G catalytic domain have been generated, but none reveal how this enzyme binds to substrate single-stranded DNA. Here, we constructed a panel of APOBEC3G amino acid substitution mutants and performed a series of biochemical, genetic, and structural assays to distinguish between “Brim” and “Kink” models for single-strand DNA binding. Each model predicts distinct sets of interactions between surface arginines and negatively charged phosphates in the DNA backbone. Concordant with both models, changing the conserved arginine at position 313 to glutamate abolished both catalytic and restriction activities. In support of the Brim model, arginine to glutamate substitutions at positions 213, 215, and 320 also compromised these APOBEC3G activities. Arginine to glutamate substitutions at Kink model residues 374 and 376 had smaller effects. These observations were supported by A3G catalytic domain-ssDNA chemical shift perturbation experiments. The overall data set is most consistent with the Brim model for single-stranded DNA binding by APOBEC3G. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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535 KiB

Open AccessArticle

Free Energy Profile of APOBEC3G Protein Calculated by a Molecular Dynamics Simulation

by Yoshifumi Fukunishi, Saki Hongo, Masami Lintuluoto and Hiroshi Matsuo

Biology 2012, 1(2), 245-259; https://doi.org/10.3390/biology1020245 - 26 Jul 2012

Viewed by 6782

Abstract

The human APOBEC3G protein (A3G) is a single-stranded DNA deaminase that inhibits the replication of retrotransposons and retroviruses, including HIV-1. Atomic details of A3G’s catalytic mechanism have started to emerge, as the structure of its catalytic domain (A3Gctd) has been revealed by NMR [...] Read more.

The human APOBEC3G protein (A3G) is a single-stranded DNA deaminase that inhibits the replication of retrotransposons and retroviruses, including HIV-1. Atomic details of A3G’s catalytic mechanism have started to emerge, as the structure of its catalytic domain (A3Gctd) has been revealed by NMR and X-ray crystallography. The NMR and crystal structures are similar overall; however, differences are apparent for β2 strand (β2) and loops close to the catalytic site. To add some insight into these differences and to better characterize A3Gctd dynamics, we calculated its free energy profile by using the Generalized-Born surface area (GBSA) method accompanied with a molecular dynamics simulation. The GBSA method yielded an enthalpy term for A3Gctd’s free energy, and we developed a new method that takes into account the distribution of the protein’s dihedral angles to calculate its entropy term. The structure solved by NMR was found to have a lower energy than that of the crystal structure, suggesting that this conformation is dominant in solution. In addition, β2-loop-β2’ configuration was stable throughout a 20-ns molecular dynamics (MD) simulation. This finding suggests that in solution A3Gctd is not likely to adopt the continuous β2 strand configuration present in the APOBEC2 crystal structure. In the NMR structure, the solvent water accessibility of the catalytic Zn²⁺ was limited throughout the 20-ns MD simulation. This result explains previous observations in which A3G did not bind or catalyze single cytosine nucleotide, even when at excessive concentrations. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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6493 KiB

Open AccessArticle

Global Conformational Dynamics of HIV-1 Reverse Transcriptase Bound to Non-Nucleoside Inhibitors

by David W. Wright, Benjamin A. Hall, Paul Kellam and Peter V. Coveney

Biology 2012, 1(2), 222-244; https://doi.org/10.3390/biology1020222 - 26 Jul 2012

Cited by 6 | Viewed by 9266

Abstract

HIV-1 Reverse Transcriptase (RT) is a multifunctional enzyme responsible for the transcription of the RNA genome of the HIV virus into DNA suitable for incorporation within the DNA of human host cells. Its crucial role in the viral life cycle has made it [...] Read more.

HIV-1 Reverse Transcriptase (RT) is a multifunctional enzyme responsible for the transcription of the RNA genome of the HIV virus into DNA suitable for incorporation within the DNA of human host cells. Its crucial role in the viral life cycle has made it one of the major targets for antiretroviral drug therapy. The Non-Nucleoside RT Inhibitor (NNRTI) class of drugs binds allosterically to the enzyme, affecting many aspects of its activity. We use both coarse grained network models and atomistic molecular dynamics to explore the changes in protein dynamics induced by NNRTI binding. We identify changes in the flexibility and conformation of residue Glu396 in the RNaseH primer grip which could provide an explanation for the acceleration in RNaseH cleavage rate observed experimentally in NNRTI bound HIV-1 RT. We further suggest a plausible path for conformational and dynamic changes to be communicated from the vicinity of the NNRTI binding pocket to the RNaseH at the other end of the enzyme. Full article

(This article belongs to the Special Issue Feature Papers)

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402 KiB

Open AccessReview

Soil Oxidation-Reduction in Wetlands and Its Impact on Plant Functioning

by S. R. Pezeshki and R. D. DeLaune

Biology 2012, 1(2), 196-221; https://doi.org/10.3390/biology1020196 - 26 Jul 2012

Cited by 198 | Viewed by 14382

Abstract

Soil flooding in wetlands is accompanied by changes in soil physical and chemical characteristics. These changes include the lowering of soil redox potential (Eh) leading to increasing demand for oxygen within the soil profile as well as production of soil phytotoxins that are [...] Read more.

Soil flooding in wetlands is accompanied by changes in soil physical and chemical characteristics. These changes include the lowering of soil redox potential (Eh) leading to increasing demand for oxygen within the soil profile as well as production of soil phytotoxins that are by-products of soil reduction and thus, imposing potentially severe stress on plant roots. Various methods are utilized for quantifying plant responses to reducing soil conditions that include measurement of radial oxygen transport, plant enzymatic responses, and assessment of anatomical/morphological changes. However, the chemical properties and reducing nature of soil environment in which plant roots are grown, including oxygen demand, and other associated processes that occur in wetland soils, pose a challenge to evaluation and comparison of plant responses that are reported in the literature. This review emphasizes soil-plant interactions in wetlands, drawing attention to the importance of quantifying the intensity and capacity of soil reduction for proper evaluation of wetland plant responses, particularly at the process and whole-plant levels. Furthermore, while root oxygen-deficiency may partially account for plant stress responses, the importance of soil phytotoxins, produced as by-products of low soil Eh conditions, is discussed and the need for development of methods to allow differentiation of plant responses to reduced or anaerobic soil conditions vs. soil phytotoxins is emphasized. Full article

(This article belongs to the Special Issue Feature Papers)

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1004 KiB

Open AccessArticle

HIV-1 Resistant CDK2-Knockdown Macrophage-Like Cells Generated from 293T Cell-Derived Human Induced Pluripotent Stem Cells

by Marina Jerebtsova, Namita Kumari, Min Xu, Gustavo Brito Alvim de Melo, Xiaomei Niu, Kuan-Teh Jeang and Sergei Nekhai

Biology 2012, 1(2), 175-195; https://doi.org/10.3390/biology1020175 - 26 Jul 2012

Cited by 12 | Viewed by 12477

Abstract

A major challenge in studies of human diseases involving macrophages is low yield and heterogeneity of the primary cells and limited ability of these cells for transfections and genetic manipulations. To address this issue, we developed a simple and efficient three steps method [...] Read more.

A major challenge in studies of human diseases involving macrophages is low yield and heterogeneity of the primary cells and limited ability of these cells for transfections and genetic manipulations. To address this issue, we developed a simple and efficient three steps method for somatic 293T cells reprogramming into monocytes and macrophage-like cells. First, 293T cells were reprogrammed into induced pluripotent stem cells (iPSCs) through a transfection-mediated expression of two factors, Oct-4 and Sox2, resulting in a high yield of iPSC. Second, the obtained iPSC were differentiated into monocytes using IL-3 and M-CSF treatment. And third, monocytes were differentiated into macrophage-like cells in the presence of M-CSF. As an example, we developed HIV-1-resistant macrophage-like cells from 293T cells with knockdown of CDK2, a factor critical for HIV-1 transcription. Our study provides a proof-of-principle approach that can be used to study the role of host cell factors in HIV-1 infection of human macrophages. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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Open AccessReview

Multi-Faceted Post-Transcriptional Functions of HIV-1 Rev

by Kuan-Teh Jeang

Biology 2012, 1(2), 165-174; https://doi.org/10.3390/biology1020165 - 23 Jul 2012

Cited by 6 | Viewed by 9225

Abstract

Post-transcriptional regulation of HIV-1 gene expression is largely governed by the activities of the viral Rev protein. In this minireview, the multiple post-transcriptional activities of Rev in the export of partially spliced and unspliced HIV-1 RNAs from the nucleus to the cytoplasm, in [...] Read more.

Post-transcriptional regulation of HIV-1 gene expression is largely governed by the activities of the viral Rev protein. In this minireview, the multiple post-transcriptional activities of Rev in the export of partially spliced and unspliced HIV-1 RNAs from the nucleus to the cytoplasm, in the translation of HIV-1 transcripts, and in the packaging of viral genomic RNAs are reviewed in brief. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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285 KiB

Open AccessReview

Breaking Barriers to an AIDS Model with Macaque-Tropic HIV-1 Derivatives

by Rajesh Thippeshappa, Hongmei Ruan and Jason T. Kimata

Biology 2012, 1(2), 134-164; https://doi.org/10.3390/biology1020134 - 5 Jul 2012

Cited by 15 | Viewed by 6718

Abstract

The development of an animal model of human immunodeficiency virus type 1 (HIV-1)/AIDS that is suitable for preclinical testing of antiretroviral therapy, vaccines, curative strategies, and studies of pathogenesis has been hampered by the human-specific tropism of HIV-1. Although simian immunodeficiency virus (SIV) [...] Read more.

The development of an animal model of human immunodeficiency virus type 1 (HIV-1)/AIDS that is suitable for preclinical testing of antiretroviral therapy, vaccines, curative strategies, and studies of pathogenesis has been hampered by the human-specific tropism of HIV-1. Although simian immunodeficiency virus (SIV) or HIV-1/SIV chimeric viruses (SHIVs)-rhesus macaque models are excellent surrogates for AIDS research, the genetic differences between SIV or SHIV and HIV-1 limit their utility as model systems. The identification of innate retroviral restriction factors has increased our understanding about blockades to HIV-1 replication in macaques and provided a guide for the construction of macaque-tropic HIV-1 clones. However, while these viruses replicate in macaque cells in vitro, they are easily controlled and have not caused AIDS in host animals, indicating that we may not fully understand the restrictive barriers of innate immunity. In this review, we discuss recent findings regarding HIV-1 restriction factors, particularly as they apply to cross-species transmission of primate lentiviruses and the development of a macaque model of HIV-1/AIDS. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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Open AccessReview

Dynamic Post-Transcriptional Regulation of HIV-1 Gene Expression

by Anna Kula and Alessandro Marcello

Biology 2012, 1(2), 116-133; https://doi.org/10.3390/biology1020116 - 3 Jul 2012

Cited by 11 | Viewed by 7944

Abstract

Gene expression of the human immunodeficiency virus type 1 (HIV-1) is a highly regulated process. Basal transcription of the integrated provirus generates early transcripts that encode for the viral products Tat and Rev. Tat promotes the elongation of RNA polymerase while Rev mediates [...] Read more.

Gene expression of the human immunodeficiency virus type 1 (HIV-1) is a highly regulated process. Basal transcription of the integrated provirus generates early transcripts that encode for the viral products Tat and Rev. Tat promotes the elongation of RNA polymerase while Rev mediates the nuclear export of viral RNAs that contain the Rev-responsive RNA element (RRE). These RNAs are exported from the nucleus to allow expression of Gag-Pol and Env proteins and for the production of full-length genomic RNAs. A balance exists between completely processed mRNAs and RRE-containing RNAs. Rev functions as an adaptor that recruits cellular factors to re-direct singly spliced and unspliced viral RNAs to nuclear export. The aim of this review is to address the dynamic regulation of this post-transcriptional pathway in light of recent findings that implicate several novel cellular cofactors of Rev function. Full article

(This article belongs to the Special Issue Structural and Molecular Biology of HIV)

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Biology, Volume 1, Issue 2 (September 2012) – 17 articles , Pages 116-459

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