DM-PhyClus: A Bayesian phylogenetic algorithm for infectious disease transmission cluster inference

Background. Conventional phylogenetic clustering approaches rely on arbitrary cutpoints applied a posteriori to phylogenetic estimates. Although in practice, Bayesian and bootstrap-based clustering tend to lead to similar estimates, they often produce conflicting measures of confidence in clusters. The current study proposes a new Bayesian phylogenetic clustering algorithm, which we refer to as DM-PhyClus, that identifies sets of sequences resulting from quick transmission chains, thus yielding easily-interpretable clusters, without using any ad hoc distance or confidence requirement. Results. Simulations reveal that DM-PhyClus can outperform conventional clustering methods, as well as the Gap procedure, a pure distance-based algorithm, in terms of mean cluster recovery. We apply DM-PhyClus to a sample of real HIV-1 sequences, producing a set of clusters whose inference is in line with the conclusions of a previous thorough analysis. Conclusions. DM-PhyClus, by eliminating the need for cutpoints and producing sensible inference for cluster configurations, can facilitate transmission cluster detection. Future efforts to reduce incidence of infectious diseases, like HIV-1, will need reliable estimates of transmission clusters. It follows that algorithms like DM-PhyClus could serve to better inform public health strategies

Role of HIV Subtype Diversity in the Development of Resistance to Antiviral Drugs

Despite the fact that over 90% of HIV-1 infected people worldwide harbor non-subtype B variants of HIV-1, knowledge of resistance mutations in non-B HIV-1 and their clinical relevance is limited. Due to historical delays in access to antiretroviral therapy (ART) on a worldwide basis, the vast majority of reports on drug resistance deal with subtype B infections in developed countries. However, both enzymatic and virological data support the concept that naturally occurring polymorphisms among different nonB subtypes can affect HIV-1 susceptibility to antiretroviral drugs (ARVs), the magnitude of resistance conferred by major mutations, and the propensity to acquire some resistance mutations. Tools need to be optimized to assure accurate measurements of drug susceptibility of non-B subtypes. Furthermore, there is a need to recognize that each subtype may have a distinct resistance profile and that differences in resistance pathways may also impact on cross-resistance and the selection of second-line regimens. It will be essential to pay attention to newer drug combinations in well designed long-term longitudinal studies involving patients infected by viruses of different subtypes

Variabilidade genética molecular em híbridos de Panicum maximum Jacq. avaliada por marcadores RAPD

Este trabalho foi realizado com o objetivo de caracterizar a diversidade genética molecular em híbridos de P. maximum Jacq. para auxiliar o programa de melhoramento dessa espécie

Highly diversified multiply drug-resistant HIV-1 quasispecies in PBMCs: a case report

© 2008 Quan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Diversidade genética entre plantas sexuais de Panicum maximum Jacq. acessada por marcadores RAPD.

O objetivo deste trabalho foi avaliar a diversidade genética entre plantas sexuais tetraploides de Panicum maximum do banco de germoplasma da Embrapa Gado de Corte, utilizando a técnica de polimorfismos de DNA amplificados ao acaso (RAPD). Quatroze plantas foram avaliadas com 17 primers. A similaridade genética foi calculada usando o coeficiente de Jaccard e o agrupamento foi feito pelo método de médias aritméticas dos pares de grupos não-balanceados (UPGMA) com base nas dissimilaridades. Uma análise de bootstrap foi feita para avaliar a consistência dos grupos formados. Um total de 145 bandas de DNA foi obtido, sendo que 128 (~88,3%) delas foram polimórficas entre as plantas estudadas. Os valores de similaridade variaram de 0,34 a 0,69. Quatro grupos foram formados e as plantas S16 e S13 não foram agrupadas com as plantas restantes, apresentando maior divergência genética. Os resultados mostram moderada diversidade genética entre as 14 plantas sexuais tetraploides de P. maximum estudadas. Os resultados obtidos podem subsidiar a escolha de progenitores para cruzamentos visando melhoramento genético da espécie.bitstream/item/71880/1/BP30.pd

Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance

<p>Abstract</p> <p>Background</p> <p>We investigated the effects of mutations K65R and K65R plus M184V on enzymatic function and mechanisms of drug resistance in subtype C reverse transcriptase (RT).</p> <p>Methods</p> <p>Recombinant subtype C HIV-1 RTs containing K65R or K65R+M184V were purified from <it>Escherichia coli</it>. Enzyme activities and tenofovir (TFV) incorporation efficiency by wild-type (WT) and mutant RTs of both subtypes were determined in cell-free assays. Efficiency of (-) ssDNA synthesis and initiation by subtype C RTs was measured using gel-based assays with HIV-1 PBS RNA template and tRNA3^Lysas primer. Single-cycle processivity was assayed under variable dNTP concentrations. Steady-state analysis was performed to measure the relative inhibitory capacity (ki/km) of TFV-disphosphate (TFV-DP). ATP-dependent excision and rescue of TFV-or ZDV-terminated DNA synthesis was monitored in time-course experiments.</p> <p>Results</p> <p>The efficiency of tRNA-primed (-)ssDNA synthesis by subtype C RTs was: WT > K65R > K65R+M184V RT. At low dNTP concentration, K65R RT exhibited lower activity in single-cycle processivity assays while the K65R+M184V mutant showed diminished processivity independent of dNTP concentration. ATP-mediated excision of TFV-or ZDV-terminated primer was decreased for K65R and for K65R+M184V RT compared to WT RT. K65R and K65R+M184V displayed 9.8-and 5-fold increases in IC50 for TFV-DP compared to WT RT. The Ki/Km of TFV was increased by 4.1-and 7.2-fold, respectively, for K65R and K65R+M184V compared to WT RT.</p> <p>Conclusion</p> <p>The diminished initiation efficiency of K65R-containing RTs at low dNTP concentrations have been confirmed for subtype C as well as subtype B. Despite decreased excision, this decreased binding/incorporation results in diminished susceptibility of K65R and K65R+M184 RT to TFV-DP.</p