Estimating time since infection in early homogeneous HIV-1 samples using a poisson model

Abstract

BackgroundThe occurrence of a genetic bottleneck in HIV sexual or mother-to-infant transmission has been well documented. This results in a majority of new infections being homogeneous, i.e., initiated by a single genetic strain. Early after infection, prior to the onset of the host immune response, the viral population grows exponentially. In this simple setting, an approach for estimating evolutionary and demographic parameters based on comparison of diversity measures is a feasible alternative to the existing Bayesian methods (e.g., BEAST), which are instead based on the simulation of genealogies.ResultsWe have devised a web tool that analyzes genetic diversity in acutely infected HIV-1 patients by comparing it to a model of neutral growth. More specifically, we consider a homogeneous infection (i.e., initiated by a unique genetic strain) prior to the onset of host-induced selection, where we can assume a random accumulation of mutations. Previously, we have shown that such a model successfully describes about 80% of sexual HIV-1 transmissions provided the samples are drawn early enough in the infection. Violation of the model is an indicator of either heterogeneous infections or the initiation of selection.ConclusionsWhen the underlying assumptions of our model (homogeneous infection prior to selection and fast exponential growth) are met, we are under a very particular scenario for which we can use a forward approach (instead of backwards in time as provided by coalescent methods). This allows for more computationally efficient methods to derive the time since the most recent common ancestor. Furthermore, the tool performs statistical tests on the Hamming distance frequency distribution, and outputs summary statistics (mean of the best fitting Poisson distribution, goodness of fit p-value, etc). The tool runs within minutes and can readily accommodate the tens of thousands of sequences generated through new ultradeep pyrosequencing technologies. The tool is available on the LANL website.

Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody

“…For all other animals, each founder was identified as a distinct, low-diversity group of sequences contained within the genetic diversity of the inoculum. Before immune selection, viral diversification follows a pattern of random mutations, which accumulate in each expanding founder population; the number and distribution of changes can be used to estimate the most recent common ancestor (22). Excluding hypermutated sequences, each lowdiversity lineage contained sequences that were either identical to the consensus of that lineage or differed by one to three nucleotides distributed over the ∼2,600-bp gene.…”

Molecular Evolution Analysis of the Human Immunodeficiency Virus Type 1 Envelope in Simian/Human Immunodeficiency Virus-Infected Macaques: Implications for Challenge Dose Selection

“…Poisson-Fitter was used to test if the Hamming distances followed a Poisson distribution and a star-like phylogeny (12). Alignments were stripped of hypermutated sequences for this analysis.…”

Pilot Studies for Development of an HIV Subtype Panel for Surveillance of Global Diversity

“…31 Plasmaand culture-derived env sequences were analyzed using Poisson-Fitter (http://www.hiv.lanl.gov/content/sequence/ POISSON_FITTER/poisson_fitter.html). 32 Recombinants were analyzed using the jumping profile hidden Markov model (jpHMM) tool provided on www.hiv.lanl.gov.…”