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David L Robertson

Publications and source records attributed to David L Robertson.

27 records · Page 2Linked to original sources
PubMed2004

Identification of a highly divergent HIV type 2 and proposal for a change in HIV type 2 classification.

We report the complete genome sequence of a highly divergent strain of human immunodeficiency virus type 2 (HIV-2), 96FR12034, identified in France from a patient of West African origin. This lineage, H, represents only the third definitive instance of a monkey-to-human transfer of SIVsm that has given rise to pathogenic HIV-2. As the different "subtypes" of HIV-2 are analogous to the different groups of HIV-1 we propose that HIV-2 subtypes henceforth by renamed groups in agreement with the HIV Nomenclature Committee. The single-strain lineages C to G and the 96FR12034 lineage identified here should be considered only as putative groups until related strains are identified that confirm circulation of these viruses in the human population.

Adult↗
PubMed2004

A link between SIVsm in sooty mangabeys (SM) in wild-living monkeys in Sierra Leone and SIVsm in an American-based SM colony.

We have developed a noninvasive method for SIVsm virion RNA detection in feces of captive sooty mangabeys (SMs) (Cercocebus atys). Employing this method to investigate the natural history of SIVsm in endangered SMs is useful for understanding the diversity and evolution of SIVsm and HIV-2. The fecal samples of 61 wild-living SMs and 14 chimpanzees (Pan troglodytes verus) were studied. Samples were collected in rural Sierra Leone in 1993. One SM sample tested positive by reverse transcriptase-PCR. No viral sequence was detected in the feces of 14 chimpanzees. Phylogenetic analysis of the env sequence obtained from SM#13 showed that it clustered within the SIVsm lineage that includes SIVsmH4, B670, and PBj, confirming a direct connection between SIVsm from West Africa and an American-based colony of SM. The virus, designated as SIVsmSL93g, supports a link between the SIVB670/SIVsmH4/SIVPbj lineage and SMs living in Northern Sierra Leone in 1993. The discovery of this strain in a wild-living SM also indicates that noninvasive methods can be used for SIV detection from monkey feces collected in the field.

Animals↗
PubMed2004

Comparative study of adaptive molecular evolution in different human immunodeficiency virus groups and subtypes.

Molecular adaptation, as characterized by the detection of positive selection, was quantified in a number of genes from different human immunodeficiency virus type 1 (HIV-1) group M subtypes, group O, and an HIV-2 subtype using the codon-based maximum-likelihood method of Yang and coworkers (Z. H. Yang, R. Nielsen, N. Goldman, and A. M. K. Pedersen, Genetics 155:431-449, 2000). The env gene was investigated further since it exhibited the strongest signal for positive selection compared to those of the other two major HIV genes (gag and pol). In order to investigate the pattern of adaptive evolution across env, the location and strength of positive selection in different HIV-1 sequence alignments was compared. The number of sites having a significant probability of being positively selected varied among these different alignment data sets, ranging from 25 in HIV-1 group M subtype A to 40 in HIV-1 group O. Strikingly, there was a significant tendency for positively selected sites to be located at the same position in different HIV-1 alignments, ranging from 10 to 16 shared sites for the group M intersubtype comparisons and from 6 to 8 for the group O to M comparisons, suggesting that all HIV-1 variants are subject to similar selective forces. As the host immune response is believed to be the dominant driving force of adaptive evolution in HIV, this result would suggest that the same sites are contributing to viral persistence in diverse HIV infections. Thus, the positions of the positively selected sites were investigated in reference to the inferred locations of different epitope types (antibody, T helper, and cytotoxic T lymphocytes) and the positions of N and O glycosylation sites. We found a significant tendency for positively selected sites to fall outside T-helper epitopes and for positively selected sites to be strongly associated with N glycosylation sites.

Adaptation, Physiological↗
PubMed2004

The molecular population genetics of HIV-1 group O.

HIV-1 group O originated through cross-species transmission of SIV from chimpanzees to humans and has established a relatively low prevalence in Central Africa. Here, we infer the population genetics and epidemic history of HIV-1 group O from viral gene sequence data and evaluate the effect of variable evolutionary rates and recombination on our estimates. First, model selection tools were used to specify suitable evolutionary and coalescent models for HIV group O. Second, divergence times and population genetic parameters were estimated in a Bayesian framework using Markov chain Monte Carlo sampling, under both strict and relaxed molecular clock methods. Our results date the origin of the group O radiation to around 1920 (1890-1940), a time frame similar to that estimated for HIV-1 group M. However, group O infections, which remain almost wholly restricted to Cameroon, show a slower rate of exponential growth during the twentieth century, explaining their lower current prevalence. To explore the effect of recombination, the Bayesian framework is extended to incorporate multiple unlinked loci. Although recombination can bias estimates of the time to the most recent common ancestor, this effect does not appear to be important for HIV-1 group O. In addition, we show that evolutionary rate estimates for different HIV genes accurately reflect differential selective constraints along the HIV genome.

Bayes Theorem↗
PubMed2003

HIV type 1 diversity in northeastern Romania in 200-2001 based on phylogenic analysis of pol sequences from patient failing antiretroviral therapy.

Protease and the first half of reverse transcriptase from 71 Romanian patients failing highly active antiretroviral therapy (HAART) have been sequenced and phylogenetically analyzed. These analyses show that 70 patients were infected with subtype F1 and one with subtype C. The pattern of drug resistance mutations in subtype F1-infected patients failing HAART is similar to that described for subtype B strains. These results show that the diversity pattern of HIV type 1 infection in Romania has remained steady over a decade, with subtype F1 remaining the predominant viral form. The circulation of subtype F1 in Romania has the potential to be a source of this HIV-1 subtype in Europe..

Adolescent↗
PubMed2003

Characterization and comparison of recombinant simian immunodeficiency virus from drill (Mandrillus leucophaeus) and mandrill (Mandrillus sphinx) isolates.

Since simian immunodeficiency virus (SIV) was found to be the source of the human AIDS pandemic, a major goal has been to characterize the diversity of SIV strains in the wild and to assess their potential for crossover into humans. In the present study, SIV was isolated from a seropositive drill (Mandrillus leucophaeus) and three seropositive mandrills (Mandrillus sphinx) by using macaque peripheral blood mononuclear cells (PBMC). Full-length sequences were obtained from a drill and mandrill and designated SIVdrl1FAO and SIVmnd5440, respectively. A 182-bp fragment of the pol genes of the two remaining mandrill SIV isolates was also analyzed. Phylogenetic analyses demonstrated that SIVdrl1FAO formed a monophyletic clade with SIVmnd5440 and SIVmndM14, recently designated SIVmnd type 2. Both the SIVdrl and SIVmnd type 2 genomes carried a vpx gene and appeared to share a common ancestor with SIVrcm in the 5' region of the genome and with SIVmndGB1 (type 1) in the 3' region of the genome. A statistically significant recombination breakpoint was detected at the beginning of envelope, suggesting that the viruses were descendents of the same recombinant. Phylogenetic analysis of vpx and vpr genes demonstrated that the vpx genes formed a monophyletic cluster that grouped with vpr from SIVagm. In addition, both SIVdrl1FAO and SIVmnd5440 replicated in human PBMC and therefore could pose a risk of transmission to the human population.

Amino Acid Sequence↗
PubMed2002

Analysis of partial pol and env sequences indicates a high prevalence of HIV type 1 recombinant strains circulating in Gabon.

Forty-one HIV-1 strains from Gabonese patients were studied according to the following strategy: nested polymerase chain reaction were performed to obtain an approximately 1,100-bp fragment containing the protease gene and the 5' half of the reverse transcriptase gene. Additional amplifications were carried out to obtain an approximately 700-bp fragment encompassing the C2V3 env gene. Fragments of 600 to 1,200 bp in the gag gene overlapping the pol sequences were used for the study of recombination patterns. Phylogenetic analyses of the different fragments were used to investigate HIV-1 diversity in Gabon. Thirty-one strains were sequenced in the env and pol genes and phylogenetic analyses classified them as subtype A (n = 2), D (n = 4), G (n = 1), H (n = 1), CRF02 (n = 8), and CRF MAL-like (n = 6); in addition, there were 6 unique recombinant forms and 1 unclassified strain, and in 2 cases pol/env sequences classified strains as subtype D whereas gag phylogeny classified them as subtype A. In 10 cases only 1 fragment was available: 4 env (2 subtype D, 1 subtype H, and 1 subtype U) and 6 pol (1 subtype A, 1 subtype C, 2 subtype G, and 2 subtype U). Minor mutations associated with viral resistance to antiretroviral drugs were observed in more than 80% of analyzed strains. Our study confirms the extensive HIV-1 diversity found in Central Africa, with more than 70% of strains from Gabon exhibiting discordant clustering in pol and env genomic regions and less than 60% concordance between sequencing and heteroduplex mobility assay genotyping. These findings highlight the fact that Central Africa represents the epicenter for the origin of HIV-1. The strategy of sequencing pol in association with env has proved to be useful for analysis of the recombinant strains. The main advantage of this approach is that it also allows for evaluation of genotypic susceptibility to antiretroviral drugs without the need for supplementary analyses.

Amino Acid Sequence↗
PubMed2002

Plasma RNA viral load in human immunodeficiency virus type 2 subtype A and subtype B infections.

Human immunodeficiency virus type 2 (HIV-2) is much less pathogenic than HIV-1, and HIV-2 infection is associated with plasma viral loads significantly lower than those found in HIV-1 infection. We have developed a real-time quantitative PCR method for measuring the HIV-2 RNA load that covers the range of genetic diversity of HIV-2 isolates and that detects extremely low viral loads. Samples from 49 patients were studied. Proviral DNA was first detected and quantified. The strains that were detected were then genotyped: 21 patients were infected with HIV-2 subtype A and 15 patients were infected with HIV-2 subtype B; 1 patient was infected with a highly divergent strain. Env PCR failed for the remaining 12 patients, so subtypes could not be determined. For viral RNA quantification, a stock of HIV-2 strain NIHZ, which was counted by electron microscopy, was used as the standard. Several primer sets targeting the highly conserved gag region were evaluated. Various primer combinations failed to amplify subtype B strains. With the final primer pair selected, which detected both subtype A and subtype B strains, the sensitivity of the assay was 100% at a viral load of 250 copies/ml and 66% at a viral load of 125 copies/ml. We found a correlation between the CD4(+)-cell count, the clinical stage, and the plasma HIV-2 RNA level. The median plasma HIV-2 RNA value for the 33 asymptomatic patients was 2.14 log(10), whereas it was 3.1 log(10) for the 16 patients with AIDS (P < 0.01). Proviral DNA was detectable in 18 symptom-free patients with high CD4(+)-cell counts, in whom viral RNA was undetectable.

Base Sequence↗