Identification and evolutionary analysis of papillomavirus sequences in New World monkeys (genera Sapajus and Alouatta) from Argentina.

OBJECTIVE: In this study, we investigated the occurrence of papillomavirus (PV) infection in non-human primates (NHPs) in northeastern Argentina. We also explored their evolutionary history and evaluated the co-speciation hypothesis in the context of primate evolution. METHODS: We obtained DNA samples from 57 individuals belonging to wild and captive populations of Alouatta caraya, Sapajus nigritus, and Sapajus cay. We assessed PV infection by PCR amplification with the CUT primer system and sequencing of 337 bp (112 amino acids) of the L1 gene. The viral sequences were analyzed by phylogenetic and Bayesian coalescence methods to estimate the time to the most common recent ancestor (tMRCA) using BEAST, v1.4.8 software. We evaluated viral/host tree congruence with TreeMap v3.0. RESULTS: We identified two novel putative PV sequences of the genus Gammapapillomavirus in Sapajus spp. and Alouatta caraya (SPV1 and AcPV1, respectively). The tMRCA of SPV1 was estimated to be 11,941,682 years before present (ybp), and that of AcPV1 was 46,638,071 ybp, both before the coalescence times of their hosts (6.4 million years ago [MYA] and 6.8 MYA, respectively). Based on the comparison of primate and viral phylogenies, we found that the PV tree was no more congruent with the host tree than a random tree would be (P > 0.05), thus allowing us to reject the model of virus-host coevolution. CONCLUSION: This study presents the first evidence of PV infection in platyrrhine species from Argentina, expands the range of described hosts for these viruses, and suggests new scenarios for their origin and dispersal.

Análisis de genomas completos de virus del papiloma humano tipo 16 y su relación con el desarrollo del cáncer de cuello de útero / Analysis of complete genomes of human papilloma virus type 16 and its relationship with cervical cancer progression

INTRODUCCIÓN El virus del papiloma humano tipo 16 (HPV-16) cumple un rol central en el desarrollo de cáncer de cuello uterino. Los HPV-16 se clasifican en variantes africanas, europeas y asiático-americanas (AA). Los estudios de asociación indican que las variantes AA son más agresivas que las europeas, pero los polimorfismos dentro del genoma aún no han sido identificados. OBJETIVOS Realizar la secuenciación del genoma completo de variantes AA de HPV-16 para comprender la patogenia, evolución y dispersión del virus en Misiones. MÉTODOS Se analizaron muestras de ADN total de células cervicales descamadas o biopsias parafinadas de 139 mujeres positivas para HPV-16 y clasificadas como: grupo control (35 mujeres, media de 29,3 años) y grupo casos (104 mujeres, media de 32,9 años). Las variantes se determinaron mediante PCR/secuenciación de 362pb de la región larga de control (LCR) viral. Para el análisis de genomas completos se empleó un protocolo de PCR diseñado en el laboratorio. Las secuencias fueron analizadas con programas bioinformáticos, y los estudios de asociación se realizaron mediante cálculo de razón de probabilidades (RP). RESULTADOS El análisis de las secuencias indicó un 93% de variantes europeas y un 7% de variantes AA, resultado que apoyaría la hipótesis de una introducción del virus durante la inmigración europea a la región. A pesar de su baja frecuencia, la infección por variantes AA se asoció con la progresión hacia el cáncer con una RP de 13,8 (1,6-117,0). El análisis preliminar de 4 genomas (>70% del genoma) indicó que todas las variantes AA presentan más de 20 aminoácidos específicos del linaje (en particular, la mutación Leu por Val en la posición 83 de la oncoproteina E6, reportada por otros autores como factor de riesgo en el desarrollo del cáncer). DISCUSIÓN Los resultados obtenidos permiten identificar factores de riesgo y generar una base de datos de secuencias para la región, útil para el monitoreo de la infección en las etapas pre y post-vacunación y como base de futuros proyectos.

TNF promoter SNP variation in Amerindians and white-admixed women from Misiones, Argentina.

The aim of this study is to describe genetic variation in the TNF promoter in the ethnically diverse population of Misiones, north-eastern Argentina. We analysed 210 women including 66 Amerindians of the Mbya-Guarani ethnic group and 144 white-admixed individuals from urban and rural areas of Misiones. Their DNA samples were surveyed for TNF polymorphisms -376 A/G, -308 A/G -244 A/G and -238 A/G by PCR amplification and direct sequencing and for the Amerindian marker -857 C/T by real-time PCR. Our main findings are as follows:(i) a distinctive pattern of Single Nucleotide Polymorphism (SNP) distribution among these groups, (ii) genetic differentiation between the Mbya-Guarani and the white-admixed populations (P < 0.05), (iii) lower gene diversity (~0.05) in Mbya-Guarani compared with the white-admixed group (~0.21); and (iv) linkage disequilibrium between the -376A and -238A SNPs in white-admixed populations. These data highlight the principal role of population history in establishing present-day genetic variation at the TNF locus and provide a framework for undertaking ethnographic and disease association studies in Misiones.

Rol del ADN mitocondrial en el cáncer de cuello de útero / Role of mitochondriaL DNA in cervical cancer

INTRODUCCIÓN La provincia de Misiones presenta una alta tasa de mortalidad por cáncer de cuello de útero (CCU). Además, la prevalencia de infección por virus del papiloma humano (VPH) descripta en las mujeres de la ciudad de Posadas y en las de las comunidades indígenas Mbya-Guaraní de la selva misionera son marcadamente diferentes (30% y 50%, respectivamente). Sin embargo, la existencia de posibles factores de riesgo genéticos, asociados al origen étnico de las poblaciones, no ha sido completamente explorada. OBJETIVOS Analizar el rol de la variación genética del ADN mitocondrial (ADNmt) en el desarrollo de lesiones de cuello de útero y CCU en una muestra de mujeres de Posadas. MÉTODOS Los linajes de ADNmt (amerindio, europeo y africano) fueron determinados mediante PCR/secuenciación del ADNmt en muestras de ADN genómico de mujeres de Posadas (81 casos y 75 controles). RESULTADOS La contribución del ADNmt al acervo genético de la ciudad fue amerindio en un 67,2%, europeo en un 26,7% y africano en un 6,1% (modelo tri-híbrido de poblaciones mixtas). Al estratificar estos resultados por grupos, se encontraron diferencias significativas en la distribución de los linajes. En particular, las lesiones de cuello de útero fueron 4 veces más frecuentes en mujeres que presentaban ADNmt no amerindio, comparadas con aquellas portadoras de mitocondrias amerindias (OR 4,4; IC95% 1,9-9,9). DISCUSIÓN El presente trabajo constituye el primer registro de un estudio de asociación entre marcadores genéticos del ADNmt y la susceptibilidad a lesiones de cuello de útero y/o riesgo de CCU en una población de alto riesgo de Argentina. Sin embargo, una importante limitación de los resultados es la existencia de posibles subestructuras poblacionales que podrían generar asociaciones espurias. El efecto de confusión de la estratificación poblacional y el linaje de ADNmt deberá ser evaluado en futuros estudios.

[Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]. / Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina.

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43%, Guarani indians: 60%, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23%) and low risk (6 y 11: 12%) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9% in urban women and 29% in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina / [Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43

, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23

) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9

in urban women and 29

in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

) and low risk (6 y 11: 12

Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina. / [Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43

, Guarani indians: 60

, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23

) and low risk (6 y 11: 12

) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9

in urban women and 29

in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.