RESUMEN
BACKGROUND: It has been reported that the increase in human immunodeficiency virus (HIV) sequence diversity in drug resistance surveillance specimens may be used to classify the duration of HIV infection as <1 or >1 year. We describe a mixed base classifier (MBC) optimized to categorize the duration of subtype B infections as <6 or >6 months on the basis of sequences for drug resistance surveillance specimens and compared MBC findings with those of serologic methods. METHODS: The behavior of the MBC was examined across a range of thresholds for calling mixed bases. MBC performance was then evaluated using either complete pol sequences or sites reflecting evolutionary pressures (HLA selection sites, sites that increased in entropy over the course of infection, and codon positions). RESULTS: The MBC performance was optimal when secondary peaks on the sequencing chromatogram accounted for at least 15% of the area of primary peaks. A cutoff of <0.45% mixed bases in the pol region best identified recent infections (sensitivity = 82.7%, specificity = 78.8%), with improvement achieved by analyzing only sites that increased in entropy. CONCLUSIONS: In an extended data set of 1354 specimens classified by BED, the optimized MBC performed significantly better than a simple MBC (agreement, 68.98% vs 67.13%). If further validated, the MBC may prove beneficial for detecting recent infection and estimating the incidence of HIV infection.
Asunto(s)
Infecciones por VIH/genética , VIH-1/genética , Área Bajo la Curva , Secuencia de Bases , Canadá/epidemiología , ARN Polimerasas Dirigidas por ADN/química , ARN Polimerasas Dirigidas por ADN/genética , Variación Genética , Infecciones por VIH/epidemiología , Humanos , Incidencia , Datos de Secuencia Molecular , ARN Viral/química , ARN Viral/genética , Curva ROC , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Análisis de Secuencia de ADN , Factores de TiempoRESUMEN
Simian foamy viruses (SFVs) infect most nonhuman primate species and appears to co-evolve with its hosts. This co-evolutionary signal is particularly strong among great apes, including orangutans (genus Pongo). Previous studies have identified three distinct orangutan SFV clades. The first of these three clades is composed of SFV from P. abelii from Sumatra, the second consists of SFV from P. pygmaeus from Borneo, while the third clade is mixed, comprising an SFV strain found in both species of orangutan. The existence of the mixed clade has been attributed to an expansion of P. pygmaeus into Sumatra following the Mount Toba super-volcanic eruption about 73,000years ago. Divergence dating, however, has yet to be performed to establish a temporal association with the Toba eruption. Here, we use a Bayesian framework and a relaxed molecular clock model with fossil calibrations to test the Toba hypothesis and to gain a more complete understanding of the evolutionary history of orangutan SFV. As with previous studies, our results show a similar three-clade orangutan SFV phylogeny, along with strong statistical support for SFV-host co-evolution in orangutans. Using Bayesian inference, we date the origin of orangutan SFV to >4.7 million years ago (mya), while the mixed species clade dates to approximately 1.7mya, >1.6 million years older than the Toba super-eruption. These results, combined with fossil and paleogeographic evidence, suggest that the origin of SFV in Sumatran and Bornean orangutans, including the mixed species clade, likely occurred on the mainland of Indo-China during the Late Pliocene and Calabrian stage of the Pleistocene, respectively.
Asunto(s)
Genes Virales , Genoma Viral , Interacciones Huésped-Patógeno/genética , Pongo/virología , Infecciones por Retroviridae/veterinaria , Virus Espumoso de los Simios/genética , Animales , Teorema de Bayes , Coevolución Biológica , Borneo/epidemiología , ADN Mitocondrial/genética , Complejo IV de Transporte de Electrones/genética , Fósiles , Expresión Génica , Historia Antigua , Indonesia/epidemiología , Pongo/clasificación , Pongo/genética , Infecciones por Retroviridae/epidemiología , Infecciones por Retroviridae/historia , Infecciones por Retroviridae/virología , Virus Espumoso de los Simios/clasificación , Erupciones Volcánicas/historiaRESUMEN
While human T-lymphotropic virus type 1 (HTLV-1) originates from ancient cross-species transmission of simian T-lymphotropic virus type 1 (STLV-1) from infected nonhuman primates, much debate exists on whether the first HTLV-1 occurred in Africa, or in Asia during early human evolution and migration. This topic is complicated by a lack of representative Asian STLV-1 to infer PTLV-1 evolutionary histories. In this study we obtained new STLV-1 LTR and tax sequences from a wild-born Bornean orangutan (Pongo pygmaeus) and performed detailed phylogenetic analyses using both maximum likelihood and Bayesian inference of available Asian PTLV-1 and African STLV-1 sequences. Phylogenies, divergence dates and nucleotide substitution rates were co-inferred and compared using six different molecular clock calibrations in a Bayesian framework, including both archaeological and/or nucleotide substitution rate calibrations. We then combined our molecular results with paleobiogeographical and ecological data to infer the most likely evolutionary history of PTLV-1. Based on the preferred models our analyses robustly inferred an Asian source for PTLV-1 with cross-species transmission of STLV-1 likely from a macaque (Macaca sp.) to an orangutan about 37.9-48.9kya, and to humans between 20.3-25.5kya. An orangutan diversification of STLV-1 commenced approximately 6.4-7.3kya. Our analyses also inferred that HTLV-1 was first introduced into Australia ~3.1-3.7kya, corresponding to both genetic and archaeological changes occurring in Australia at that time. Finally, HTLV-1 appears in Melanesia at ~2.3-2.7kya corresponding to the migration of the Lapita peoples into the region. Our results also provide an important future reference for calibrating information essential for PTLV evolutionary timescale inference. Longer sequence data, or full genomes from a greater representation of Asian primates, including gibbons, leaf monkeys, and Sumatran orangutans are needed to fully elucidate these evolutionary dates and relationships using the model criteria suggested herein.
Asunto(s)
Evolución Biológica , Infecciones por Deltaretrovirus/transmisión , Virus Linfotrópico T Tipo 1 Humano/genética , Filogenia , Virus Linfotrópico T Tipo 1 de los Primates/genética , Virus Linfotrópico T Tipo 1 de los Simios/genética , Animales , Secuencia de Bases , Teorema de Bayes , Infecciones por Deltaretrovirus/epidemiología , Infecciones por Deltaretrovirus/historia , Infecciones por Deltaretrovirus/virología , Productos del Gen tax/genética , Historia Antigua , Virus Linfotrópico T Tipo 1 Humano/clasificación , Humanos , Macaca/virología , Tasa de Mutación , Paleontología , Pongo pygmaeus/virología , Virus Linfotrópico T Tipo 1 de los Primates/clasificación , Virus Linfotrópico T Tipo 1 de los Simios/clasificación , Secuencias Repetidas TerminalesRESUMEN
Host immune selection pressure influences the development of mutations that allow for HIV escape. Mutation patterns induced in HIV by the human leukocyte antigen (HLA) are HLA-allele specific. As ethnic groups have distinct and characteristic HLA allele frequencies, we can expect divergent viral evolution within ethnicities. Here, we have sequenced and analyzed the HIV pol gene from 1248 subtype B infected, treatment-naïve individuals in Canada. Phylogenetic analysis showed no separation between pol sequences from five self-identified ethnic groups, yet fixation index (F(ST)) values showed significant divergence between ethnicities. A total of 17 amino acid sites showed an ethnic-specific fixation pattern (0.015Asunto(s)
Adaptación Fisiológica/genética
, Epítopos/inmunología
, Evolución Molecular
, Infecciones por VIH/etnología
, VIH-1/genética
, VIH-1/patogenicidad
, Antígenos HLA/inmunología
, Adulto
, Alelos
, Canadá/etnología
, Femenino
, Infecciones por VIH/inmunología
, Infecciones por VIH/virología
, Antígenos HLA/genética
, Humanos
, Masculino
, Persona de Mediana Edad
, Selección Genética
, Adulto Joven