RESUMEN
HIV-2 and SIVMAC are AIDS-causing, zoonotic lentiviruses that jumped to humans and rhesus macaques, respectively, from SIVSM-bearing sooty mangabey monkeys. Cross-species transmission events such as these sometimes necessitate virus adaptation to species-specific, host restriction factors such as TRIM5. Here, a new human restriction activity is described that blocks viruses of the SIVSM/SIVMAC/HIV-2 lineage. Human T, B, and myeloid cell lines, peripheral blood mononuclear cells and dendritic cells were 4 to >100-fold less transducible by VSV G-pseudotyped SIVMAC, HIV-2, or SIVSM than by HIV-1. In contrast, transduction of six epithelial cell lines was equivalent to that by HIV-1. Substitution of HIV-1 CA with the SIVMAC or HIV-2 CA was sufficient to reduce HIV-1 transduction to the level of the respective vectors. Among such CA chimeras there was a general trend such that CAs from epidemic HIV-2 Group A and B isolates were the most infectious on human T cells, CA from a 1° sooty mangabey isolate was the least infectious, and non-epidemic HIV-2 Group D, E, F, and G CAs were in the middle. The CA-specific decrease in infectivity was observed with either HIV-1, HIV-2, ecotropic MLV, or ALV Env pseudotypes, indicating that it was independent of the virus entry pathway. As2O3, a drug that suppresses TRIM5-mediated restriction, increased human blood cell transduction by SIVMAC but not by HIV-1. Nonetheless, elimination of TRIM5 restriction activity did not rescue SIVMAC transduction. Also, in contrast to TRIM5-mediated restriction, the SIVMAC CA-specific block occurred after completion of reverse transcription and the formation of 2-LTR circles, but before establishment of the provirus. Transduction efficiency in heterokaryons generated by fusing epithelial cells with T cells resembled that in the T cells, indicative of a dominant-acting SIVMAC restriction activity in the latter. These results suggest that the nucleus of human blood cells possesses a restriction factor specific for the CA of HIV-2/SIVMAC/SIVSM and that cross-species transmission of SIVSM to human T cells necessitated adaptation of HIV-2 to this putative restriction factor.
Asunto(s)
Antivirales/farmacología , Cápside/microbiología , VIH-2/efectos de los fármacos , Leucocitos Mononucleares/virología , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Integración Viral/efectos de los fármacos , Animales , Línea Celular , Células Dendríticas/efectos de los fármacos , Células Dendríticas/virología , VIH-2/genética , VIH-2/inmunología , Humanos , Leucocitos Mononucleares/inmunología , Virus de la Inmunodeficiencia de los Simios/genética , Linfocitos T/efectos de los fármacos , Linfocitos T/virologíaRESUMEN
Los problemas virales reducen los rendimientos y la calidad del tubérculo semilla en cultivos de papa de todo el mundo. Esta investigación se planteó con el fin de evaluar los niveles de incidencia de potyvirus en diez de las principales regiones cultivadoras de papa de los departamentos de Antioquia, Boyacá, Cundinamarca y Nariño (Colombia), y las características genotípicas del virus Y de la papa (Potato virus Y, PVY), seleccionado por ser el potyvirus más limitante de este cultivo. Para la evaluación de la incidencia se utilizaron pruebas de Elisa con anticuerpos que reconocen epítopes comunes a los potyvirus, mientras que las pruebas moleculares incluyeron el análisis filogenético de secuencias parciales del gen de la cápside viral de 33 aislamientos, así como la secuenciación de una porción de los extremos 5´ y 3´del genoma de dos cepas colombianas de este virus. Los resultados confirmaron la presencia de potyvirus en los cultivos de los cuatro departamentos evaluados, con una incidencia promedio del 72%, siendo este nivel superior al 56% en todas las zonas evaluadas. Los análisis moleculares del PVY, permitieron asociar las cepas colombianas estudiadas con las razas PVYN y la variante PVYNTN, esta última responsable de la enfermedad conocida en el mundo como PTNRD (Potato tuber necrotic ringspot disease).
Potato viruses are responsible for significant reductions in seed quality and crop yields around the world. In this study, we evaluate the levels of incidence of potyvirus in ten potato growing regions of Colombia from the provinces of Antioquia, Boyacá, Cundinamarca and Nariño. As PVY is the most limiting potyvirus in potato farming, a molecular characterization of Colombian PVY strains was also performed. Incidence was evaluated by ELISA using general potyvirus antibodies. Phylogenetic analysis were made on the partial sequence of the capsid gene from 33 isolates. A portion of the 5´ and 3' genome ends was obtained from two Colombian strains. Results confirmed the presence of potyvirus in the four provinces with an average incidence of 72%. The lowest incidence value was 56%. Molecular analysis clustered all Colombian isolates with strains PVYN and PVYNTN, the latter responsible for the disease known as PTNRD (Potato tuber necrotic ringspot disease).