Dataset Information

Molecular cloning of two west African human immunodeficiency virus type 2 isolates that replicate well in macrophages: a Gambian isolate, from a patient with neurologic acquired immunodeficiency syndrome, and a highly divergent Ghanian isolate.

ABSTRACT: Human immunodeficiency virus type 2 (HIV-2)-related viruses were isolated from a Gambian dying of exclusively neurological disease (HIV-2D194) and from an asymptomatic Ghanian (HIV-2D205). Both strains exhibited properties of HIV-1 biological subtype c: they grew slowly and induced few or no syncytia but eventually produced high levels of particle-associated reverse transcriptase in cultures of fresh peripheral blood lymphocytes, and they established stable infection of T-lymphoma (HUT-78) and monocytic (U937) cell lines. Each produced even higher levels of reverse transcriptase when fresh human monocytes/macrophages were used as target cells. The viruses were molecularly cloned after a single passage in culture, in order to minimize in vitro selection of subtypes present in vivo. Restriction-site analysis showed heterogeneity within each isolate. Nucleotide sequence analysis of a portion of the HIV-2D194 genome revealed that it is a member of the prototypic HIV-2 family, displaying 13% divergence versus HIV-2ROD and HIV-2NIHZ, as compared to 9% divergence between HIV-2ROD and HIV-2NIHZ. In contrast, HIV-2D205 is the most highly divergent HIV-2 strain yet described: it is equidistant in relation between the known HIV-2 strains and the simian immunodeficiency virus isolates from rhesus macaque monkeys (23-25% divergence).

SUBMITTER: Kuhnel H

PROVIDER: S-EPMC286917 | biostudies-other | 1989 Apr

REPOSITORIES: biostudies-other

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Molecular cloning of two west African human immunodeficiency virus type 2 isolates that replicate well in macrophages: a Gambian isolate, from a patient with neurologic acquired immunodeficiency syndrome, and a highly divergent Ghanian isolate.

Kühnel H H von Briesen H H Dietrich U U Adamski M M Mix D D Biesert L L Kreutz R R Immelmann A A Henco K K Meichsner C C

Proceedings of the National Academy of Sciences of the United States of America 19890401 7

Human immunodeficiency virus type 2 (HIV-2)-related viruses were isolated from a Gambian dying of exclusively neurological disease (HIV-2D194) and from an asymptomatic Ghanian (HIV-2D205). Both strains exhibited properties of HIV-1 biological subtype c: they grew slowly and induced few or no syncytia but eventually produced high levels of particle-associated reverse transcriptase in cultures of fresh peripheral blood lymphocytes, and they established stable infection of T-lymphoma (HUT-78) and m ...[more]

PMID: 2467304

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Project description:In tropical forests, anthropogenic activities are major drivers of the destruction and degradation of natural habitats, causing severe biodiversity loss. African colobine monkeys (Colobinae) are mainly folivore and strictly arboreal primates that require large forests to subsist, being among the most vulnerable of all nonhuman primates. The Western red colobus Piliocolobus badius and the King colobus Colobus polykomos inhabit highly fragmented West African forests, including the Cantanhez Forests National Park (CFNP) in Guinea-Bissau. Both species are also found in the largest and best-preserved West African forest-the Taï National Park (TNP) in Ivory Coast. Colobine monkeys are hunted for bushmeat in both protected areas, but these exhibit contrasting levels of forest fragmentation, thus offering an excellent opportunity to investigate the importance of well-preserved forests for the maintenance of evolutionary potential in these arboreal primates. We estimated genetic diversity, population structure, and demographic history by using microsatellite loci and mitochondrial DNA. We then compared the genetic patterns of the colobines from TNP with the ones previously obtained for CFNP and found contrasting genetic patterns. Contrary to the colobines from CFNP that showed very low genetic diversity and a strong population decline, the populations in TNP still maintain high levels of genetic diversity and we found no clear signal of population decrease in Western red colobus and a limited decrease in King colobus. These results suggest larger and historically more stable populations in TNP compared to CFNP. We cannot exclude the possibility that the demographic effects resulting from the recent increase of bushmeat hunting are not yet detectable in TNP using genetic data. Nevertheless, the fact that the TNP colobus populations are highly genetically diverse and maintain large effective population sizes suggests that well-preserved forests are crucial for the maintenance of populations, species, and probably for the evolutionary potential in colobines.

Project description:We aimed in this study to describe efavirenz concentration-time courses in treatment-naïve children after once-daily administration to study the effects of age and body weight on efavirenz pharmacokinetics and to test relationships between doses, plasma concentrations, and efficacy. For this purpose, efavirenz concentrations in 48 children were measured after 2 weeks of didanosine-lamivudine-efavirenz treatment, and samples were available for 9/48 children between months 2 and 5 of treatment. Efavirenz concentrations in 200 plasma specimens were measured using a validated high-performance liquid chromatography method. A population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. The estimated minimal and maximal concentrations of efavirenz in plasma (Cmin and Cmax, respectively) and the area under the concentration-time curve (AUC) were correlated to the decrease in human immunodeficiency virus type 1 RNA levels after 3 months of treatment. The threshold Cmin (and AUC) that improved efficacy was determined. The target minimal concentration of 4 mg/liter was considered for toxicity. An optimized dosing schedule that would place the highest percentage of children in the interval of effective and nontoxic concentrations was simulated. The pharmacokinetics of efavirenz was best described by a one-compartment model with first-order absorption and elimination. The mean apparent clearance and volume of distribution for efavirenz were 0.211 liter/h/kg and 4.48 liters/kg, respectively. Clearance decreased significantly with age. When the recommended doses were given to 46 of the 48 children, 19% (44% of children weighing less than 15 kg) had C(min)s below 1 mg/liter. A significantly higher percentage of children with C(min)s of >1.1 mg/liter or AUCs of >51 mg/liter x h than of children with lower values had viral load decreases greater than 2 log10 copies/ml after 3 months of treatment. Therefore, to optimize the percentage of children with C(min)s between 1.1 and 4 mg/liter, children should receive the following once-daily efavirenz doses: 25 mg/kg of body weight from 2 to 6 years, 15 mg/kg from 6 to 10 years, and 10 mg/kg from 10 to 15 years. These assumptions should be prospectively confirmed.

Dataset Information

Molecular cloning of two west African human immunodeficiency virus type 2 isolates that replicate well in macrophages: a Gambian isolate, from a patient with neurologic acquired immunodeficiency syndrome, and a highly divergent Ghanian isolate.

Publications

Molecular cloning of two west African human immunodeficiency virus type 2 isolates that replicate well in macrophages: a Gambian isolate, from a patient with neurologic acquired immunodeficiency syndrome, and a highly divergent Ghanian isolate.

Similar Datasets

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