RESUMEN
MuV caused three epidemic waves in Spain since genotype G emerged in 2005, despite high vaccination coverage. SH gene sequencing according to WHO protocols allowed the identification of seven relevant variants and 88 haplotypes. While the originally imported MuVi/Sheffield.GBR/1.05/-variant prevailed during the first two waves, it was subsequently replaced by other variants originated by either local evolution or importation, according to the additional analysis of hypervariable NCRs. The time of emergence of the MRCA of each MuV variant clade was concordant with the data of the earliest sequence. The analysis of Shannon entropy showed an accumulation of variability on six particular positions as the cause of the increase on the number of circulating SH variants. Consequently, SH gene sequencing needs to be complemented with other more variable markers for mumps surveillance immediately after the emergence of a new genotype, but the subsequent emergence of new SH variants turns it unnecessary.
Asunto(s)
Virus de la Parotiditis , Paperas , Humanos , Virus de la Parotiditis/genética , España/epidemiología , Filogenia , Paperas/epidemiología , Paperas/prevención & control , GenotipoRESUMEN
OBJECTIVES: The long-term non-progressors (LTNPs) are a heterogeneous group of HIV-positive individuals characterized by their ability to maintain high CD4+ T-cell counts and partially control viral replication for years in the absence of antiretroviral therapy. The present study aims to identify host single nucleotide polymorphisms (SNPs) associated with non-progression in a cohort of 352 individuals. METHODS: DNA microarrays and exome sequencing were used for genotyping about 240 000 functional polymorphisms throughout more than 20 000 human genes. The allele frequencies of 85 LTNPs were compared with a control population. SNPs associated with LTNPs were confirmed in a population of typical progressors. Functional analyses in the affected gene were carried out through knockdown experiments in HeLa-P4, macrophages and dendritic cells. RESULTS: Several SNPs located within the major histocompatibility complex region previously related to LTNPs were confirmed in this new cohort. The SNP rs1127888 (UBXN6) surpassed the statistical significance of these markers after Bonferroni correction (q = 2.11 × 10-6). An uncommon allelic frequency of rs1127888 among LTNPs was confirmed by comparison with typical progressors and other publicly available populations. UBXN6 knockdown experiments caused an increase in CAV1 expression and its accumulation in the plasma membrane. In vitro infection of different cell types with HIV-1 replication-competent recombinant viruses caused a reduction of the viral replication capacity compared with their corresponding wild-type cells expressing UBXN6. CONCLUSIONS: A higher prevalence of Ala31Thr in UBXN6 was found among LTNPs within its N-terminal region, which is crucial for UBXN6/VCP protein complex formation. UBXN6 knockdown affected CAV1 turnover and HIV-1 replication capacity.
Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Relacionadas con la Autofagia/genética , Progresión de la Enfermedad , Estudios de Asociación Genética , Infecciones por VIH/genética , Polimorfismo de Nucleótido Simple , Caveolina 1/genética , Estudios de Cohortes , Células Dendríticas/virología , Frecuencia de los Genes , Técnicas de Silenciamiento del Gen , Infecciones por VIH/virología , Sobrevivientes de VIH a Largo Plazo , VIH-1 , Células HeLa , Humanos , Macrófagos/virología , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Secuenciación del ExomaRESUMEN
Porcine reproductive and respiratory syndrome virus (PRRSV) isolates are classified in two different genotypes, based on genomic heterogeneity: type 1, which comprises European type isolates, and type 2, which includes North American type isolates. It is believed that members of both genotypes differ in some biological properties including pathogenicity, however extensive studies comparing isolates of both genotypes have never been carried out. The objective of the present study was to compare the pathogenic properties of six different PRRSV isolates, three of type 1 and three of type 2, in a young pig infection model. For this purpose, a total of 105 3-week-old piglets were divided in 7 groups of 15 animals that were exposed on day 0 of the experiment to one of the six isolates tested or were mock infected (negative control group). Clinical signs and rectal temperatures were recorded daily and blood samples were taken on days 3, 6, 9, 12, 15, 18 and 21 of the experiment. On days 7, 14 and 21 post-inoculation five animals per group were sacrificed, macroscopic lung lesions were evaluated and different tissue samples were collected to determine viral organic distribution. The results obtained indicate that type 2 isolates are more pneumovirulent than type 1 isolates, as demonstrated by the recording of respiratory clinical signs only in pigs exposed to type 2 viruses and by the severity of macroscopic and microscopic lung lesions in those pigs. However, no clear differences could be established between genotypes in systemic clinical signs or viral load and viral distribution after challenge. These results support the general idea that type 2 isolates induce more severe respiratory disease than type 1 isolates.