HIV-1 Genetic Diversity, Volume II

HIV-1 Genetic Diversity, Volume II PDF Author: Kok Keng Tee
Publisher: Frontiers Media SA
ISBN: 2889769402
Category : Science
Languages : en
Pages : 260

Get Book Here

Book Description

HIV-1 Genetic Diversity, Volume II

HIV-1 Genetic Diversity, Volume II PDF Author: Kok Keng Tee
Publisher: Frontiers Media SA
ISBN: 2889769402
Category : Science
Languages : en
Pages : 260

Get Book Here

Book Description


HIV-1 Genetic Diversity

HIV-1 Genetic Diversity PDF Author: Kok Keng Tee
Publisher: Frontiers Media SA
ISBN: 2889668991
Category : Science
Languages : en
Pages : 222

Get Book Here

Book Description


Genetic Diversity of HIV

Genetic Diversity of HIV PDF Author: African Services Committee
Publisher:
ISBN:
Category :
Languages : en
Pages : 11

Get Book Here

Book Description


Decoding Diversity Understanding Novel Mutations in HIV-1 Rev and LTR Genes

Decoding Diversity Understanding Novel Mutations in HIV-1 Rev and LTR Genes PDF Author: Itachi Publications
Publisher: Itachi Publications
ISBN: 9783763043071
Category : Health & Fitness
Languages : en
Pages : 0

Get Book Here

Book Description
Human Immunodeficiency Virus (HIV) belongs to the Retroviridae family and the sub family Lentivirinae. Infection with HIV usually culminates in AIDS over a variable period of time. AIDS stands for Acquired Immunodeficiency Syndrome. HIV primarily infects critical cells in the human immune system such as helper T cells (specifically CD4 T cells, macrophages, and dendritic cells). The infection results in the loss of natural defense against trivial infections and makes the patient susceptible to various opportunistic infections resulting in the eventual death of the patient. HIV has a diploid RNA genome encoding nine viral proteins. HIV-1, demonstrates high genetic diversity due to lack of proof reading ability of its enzyme, reverse transcriptase. Although the HIV-1 epidemic in India is mainly due to subtype C, other subtypes have also been reported from different parts of India. To combat the infection and for the development of new anti-viral strategies, it is necessary to appreciate the extent of naturally found variations in HIV-1 genes. The focus of the present work was to study the naturally occurring novel mutations in HIV-1 Rev. LTR, Nef and Vpu genes. Since Rev is an important regulatory gene of HIV-1 genome for expression of HIV-1 structural proteins and production of genomic RNA. We first study the genetic and functional characterization of HIV-1 Rev derived from HIV-1 infected individuals in North India to find out the levels of genetic changes and to determine their functional relevance.

HIV-1 Group O Genetic Diversity

HIV-1 Group O Genetic Diversity PDF Author: Marie Leoz
Publisher:
ISBN:
Category :
Languages : fr
Pages : 15

Get Book Here

Book Description
Les VIH-1 de groupe 0 (VIH-1/0) sont des variants rares, essentiellement retrouvés au Cameroun où ils représenteraient plusieurs milliers de cas. Les causes de leur faible diffusion restent méconnues: leur émergence serait aussi ancienne que les VIH-1 de groupe M, pourtant devenus pandémiques. En près d'un siècle, les VIII-1/0 ont développé une importante diversité génétique, dont la description reste ambiguë du fait de l'existence de plusieurs nomenclatures basées sur un nombre restreint de séquences génétiques. Peu de données sont disponibles quant aux causes de cette diversité et à son impact sur diverses propriétés virologiques. La mutation Y181C de la Transcriptase Inverse (TI) a toutefois été proposée comme critère de classification des VIH-1/0, et suspectée de conférer un avantage réplicatif à ceux chez qui elle serait naturellement présente. Ce travail a donc constitué à caractériser plus largement la diversité génétique des vm-vo, et à explorer la dynamique de leur évolution au cours du temps à l'aide de méthodes bayésiennes. Nous avons ainsi identifié deux phases de diversification successives, liées au développement de deux sous-groupes: T, minoritaire et ayant émergé dans les années 1960, et H, majoritaire et ayant émergé du sous-groupe T dans les années 1980. La présence de la mutation 181C a été associée au sous-groupe H, ce qui a conduit à la définition de trois populations virales: H/181C-like, H/181Y-like et T/181Y-like. Une forte conservation du motif signature K28, K103, 1142, D174, L178 au niveau de la poche non catalytique de la TI des virus H/181C-like a été mise en évidence, mais aucun de ces marqueurs (présence de la mutation 181C, appartenance à la population H/181C-like ou présence du motif associé) ne semble être lié à un plus haut niveau de réplication virale in vivo. Afin de développer les connaissances sur le tropisme des VIH-110, une propriété en lien avec l'évolution 1 clinique de l'infection par VIH-11M ou VIH-2, nous avons développé un outil de phénotropisme basé sur la production de pseudovirus présentant un clone de glycoprotéine d'Enveloppe V111-1/0. Nous avons montré que les 16 Enveloppes produites n'utilisaient que le corécepteur CCR5, malgré l'exploration d'échantillons séquentiels et/ou prélevés en phase d'infection tardive. Enfin, pour permettre l'analyse des propriétés phénotypiques liées aux différentes populations VIH-1/0, nous avons participé à la production de trois nouveaux de clones moléculaires infectieux représentant deux souches H/181C-like et une souche T/181Y-like. Ces clones ont contribué à démontrer comment les VIH-1/0 contrecarraient l'action de la Tetherine et modulaient l'expression de NFKB par le biais des protéines Nef et Vpu. En conclusion, nos résultats suggèrent une dynamique d'évolution des V111-1/0 plus complexe que suspectée jusqu'alors, ayant entraîné l'émergence de deux sous-groupes distincts. Nous avons unifié les 1 différents systèmes de nomenclature, décrit des caractéristiques distinguant trois populations virales, et développé de nouveaux outils pour contribuer à une meilleure connaissance des conséquences de leur diversité génétique.

HIV-1 Quasispecies Heterogeneity Mediates Tat Function, Molecular Epistasis, and Neuropathogenesis

HIV-1 Quasispecies Heterogeneity Mediates Tat Function, Molecular Epistasis, and Neuropathogenesis PDF Author: Cassandra Spector
Publisher:
ISBN:
Category : HIV (Viruses)
Languages : en
Pages : 0

Get Book Here

Book Description
Over 38 million people worldwide continue to live with human immunodeficiency virus type 1 (HIV-1). HIV-1 remains a major public health concern due to chronic infection that cannot be cured by conventional antiretroviral therapies (ART). Infected cells continue to produce and secrete viral proteins, including the transactivator of transcription (Tat), even in viral load suppressed individuals. This predisposes people with HIV (PWH) to increased risk for developing HIV-1-associated comorbidities, such as HIV-1-associated neurocognitive disorder (HAND). The HIV-1 genome is susceptible to genetic diversification due to the error prone viral reverse transcriptase, as well as from adaptation in response to host restriction factors and immune selection pressures. This results in the formation of unique viral quasispecies (vQS) populations in individuals. Genetic variation within vQS may manifest in Tat as functional amino acid (AA) mutations. Tat's canonical function is to bind host factors and the HIV-1 transcription response element (TAR) RNA to enhance viral transcription efficiency, but also participates in pathogenic activities that contribute to overall HIV-1 pathogenesis and comorbidities. Previous studies have sought to characterize functional genetic variation between both Tat exons, which are separated by about 3 kilobases in the HIV-1 genome. However, prior sequencing technologies could not associate observed variants within and between exons from the same molecule of DNA. Therefore, the Pacific Biosciences (PacBio) Sequel platform was utilized to obtain long read sequences encompassing both Tat exons. PBMC gDNA from therapy-controlled participants of the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort was used to isolate tat-containing 4 kilobase amplicons to be sequenced. This sequencing dataset allowed for studies on viral diversity, co-occurring AAs, and functional conservation in Tat. Though deviations from expected occurrence composed a small proportion of observed co-variants, these presented potential variants of interest for future studies. AA functional sequence analyses displayed two patterns of conserved activity split across annotated Tat functions and demonstrated heterogeneity of Tat functional ability between vQS populations. Sequencing data from this study was applied to questions involving Tat's interactions with other viral proteins and its role in neuropathogenesis. Given the observed genetic diversity within tat, further studies investigated selection pressure between tat and rev, another HIV-1 gene that encodes a transcriptional regulatory protein and shares an overlapping reading frame with tat. Selection pressures observed on each overlapping gene segment as well as on individual overlapping codons supported the presence of segregated functional domain organization between the two genes. AA sequence logos of each gene further suggested adaptation of AAs that overlapped with functionally essential AAs in the opposite protein. To address the contribution of Tat AA variation to occurrence of HAND, Tat vQS sequences were associated with paired neuropsychological assessment test data administered to CARES Cohort participants. Neurocognitive phenotypes emerged that were led by dominant deficits in neurocognitive domains. Vectorization and dimensional reduction of Tat sample-specific sequences overlayed with domain deficit scores showed that sequence similarity between participants also associated with neurocognitive impairment in certain domains. Overall, these studies have led to advances in understanding Tat vQS composition and protein function in PWH. The data and results were applied to address questions on pathogenic mechanisms and the development of HIV-1 comorbidities involving Tat.

HIV -specific CD8+ T Cell Phenotype and HIV-1 Genetic Diversity

HIV -specific CD8+ T Cell Phenotype and HIV-1 Genetic Diversity PDF Author: Lyle McKinnon
Publisher:
ISBN:
Category :
Languages : en
Pages : 265

Get Book Here

Book Description


HIV-1 Genetic Diversity, Evolution and Neuropsychological Impairment

HIV-1 Genetic Diversity, Evolution and Neuropsychological Impairment PDF Author: George Kimet Hightower
Publisher:
ISBN: 9781267333858
Category :
Languages : en
Pages : 72

Get Book Here

Book Description
HIV-1 associated neurocognitive disorders (HAND) remain a significant problem worldwide and can range in severity from disabling dementia to asymptomatic cognitive, motor and behavioral changes. Clinical assessments are the gold standard for detecting impairment and have defined the scope and severity of HAND; however, the viral determinants of HAND are not well understood. To further characterize the viral determinants of HAND, we studied viral evolution and disease by analyzing HIV-1 RNA extracted from blood and CSF samples along with participant specific clinical and neuropsychological assessments. HIV-1 RNA was amplified with Polymerase Chain Reaction (PCR) and sequenced using the Sanger Method. Neuropsychological assessments were administered and scored by trained psychometrists and included seven ability domains: learning, delayed recall, verbal fluency, processing speed, attention/working memory, abstraction/executive functioning and motor speed. HIV-1 population diversity was positively associated with disease, specifically AIDS and neuropsychological impairment. Further, antiretroviral resistance was associated with lower CSF viral loads and with better neuropsychological performance. Our findings suggest that HIV-1 virulence is most likely associated with the capacity of a viral population to maintain genetic diversity and not simply a specific and predominant genotypic variant. Although, the exact underlying mechanism for this remains unclear, complex phenotypes such as neuropsychological impairment may result from different HIV-1 variants operating in a coordinated manner to cause disease.

AIDS and Other Manifestations of HIV Infection

AIDS and Other Manifestations of HIV Infection PDF Author: Gary P. Wormser
Publisher: Raven Press (ID)
ISBN:
Category : Medical
Languages : en
Pages : 748

Get Book Here

Book Description
Provides an update on AIDS and other HIV infections. Over 40 chapters present information on the biological properties of the etiologic viral agent, its clinico-pathological manifestations, the epidemiology of HIV infection and the day-to-day management of HIV infected patients.

HIV and the New Viruses

HIV and the New Viruses PDF Author: Angus G. Dalgleish
Publisher: Elsevier
ISBN: 0080534082
Category : Medical
Languages : en
Pages : 569

Get Book Here

Book Description
HIV and the New Viruses presents cutting-edge reviews of persistent human virus infections as a coherent collection for the first time. These cover recently discovered viruses such as HHV-6, HHV-8 and HCV, as well as the latest research on HIV. This comprehensive and updated reference includes an in-depth study of the major issues in the epidemiology, pathogenicity, molecular virology, host responses and management of conditions associated with those viruses. Information on new pharmaceuticals and vaccine developments is also included. Edited by the leading experts in the field, HIV and the New Viruses will be essential reading for postgraduates, clinicians and researchers in virology, immunology, cancer, molecular biology and the pharmaceutical industry. Presents cutting-edge reviews of persistent human virus infections as a coherent collection for the first time Includes an in-depth study of the major issues in the epidemiology, pathogenicity, molecular virology, host responses, and management of conditions associated with those viruses