Cut site preference allows influenza A virus PA-X to discriminate between host and viral mRNAs.

Many viruses block host gene expression to take over the infected cell. This process, termed host shutoff, is thought to promote viral replication by preventing antiviral responses and redirecting cellular resources to viral processes. Several viruses from divergent families accomplish host shutoff through RNA degradation by endoribonucleases. However, viruses also need to ensure expression of their own genes. The influenza A virus endoribonuclease PA-X solves this problem by sparing viral mRNAs and some host RNAs necessary for viral replication. To understand how PA-X distinguishes between RNAs, we characterized PA-X cut sites transcriptome-wide using 5' rapid amplification of complementary DNA ends coupled to high-throughput sequencing. This analysis, along with RNA structure predictions and validation experiments using reporters, shows that PA-Xs from multiple influenza strains preferentially cleave RNAs at GCUG tetramers in hairpin loops. Importantly, GCUG tetramers are enriched in the human but not the influenza transcriptome. Moreover, optimal PA-X cut sites inserted in the influenza A virus genome are quickly selected against during viral replication in cells. This finding suggests that PA-X evolved these cleavage characteristics to preferentially target host over viral mRNAs in a manner reminiscent of cellular self versus non-self discrimination.

[Prevalence of hepatitis virus infection markers in HIV-infected patients in Southern Spain]. / Prevalencia de los marcadores de infección de los virus de las hepatitis en pacientes portadores del VIH en el sur de España.

OBJECTIVES: To determine: (a) The prevalence of active infection by the hepatitis C virus (HCV) and hepatitis B virus (HBV) in HIV-infected patients, as well as previous exposure to hepatitis A virus (HAV), HBV and HCV. (b) The proportion of patients who have been vaccinated against HAV and/or HBV. (c) The HCV genotype distribution and the percentage of patients who have started treatment against HCV infection. METHODS: All HIV-infected patients who attended the Infectious Diseases Unit of a tertiary care hospital in Southern Spain between September 2008 and February 2009 were included in a prospective cross-sectional study. RESULTS: A total of 520 patients were included. Three hundred and fifty-eight (69%) patients had positive HCV antibody, while 71% of them showed detectable HCV-RNA. The HCV genotype distribution was: 153 (62%) genotype 1, 49 (20%) genotype 3, and 45 (18%) genotype 4. One hundred and thirteen (36.5%) subjects had received treatment against HCV. The prevalence of active HBV infection was 4.4%, while the exposure to HBV was 54.8%. Four hundred and thirty-seven (84%) patients had positive markers of infection of HAV. Of the patients eligible to be vaccinated, 25.6% and 22.3% patients were vaccinated against HAV and HBV, respectively. CONCLUSIONS: The current prevalence of active HCV infection remains high in our area. There were no changes in the HCV genotype distribution. The number of patients with indication for HBV and HAV vaccination and receive these vaccines is low.

Interleukin 28B rs12979860 (CT/TT) genotype is associated with milder hepatic damage in the natural evolution of HCV/HIV coinfection.

Hepatitis C virus (HCV)/human immunodefficiency virus (HIV) coinfection is a major health problem, affecting mostly to individuals with exposure to blood products, as hemophiliacs or intravenous drug users, or those exposed to high-risk sexual practices. Genotyping of interleukin 28B (IL-28B) rs12979860 polymorphism is a useful tool for guiding therapeutic decisions in this disease. On the contrary, there is not enough information on the pathogenic role of this polymorphism in the natural history of the disease. The objective of this study is to describe the relationships between the CT/TT genotype of this polymorphism with viral loads and also with a number of biomarkers of liver function in coinfected patients naïve for treatment for HCV. Seventy-five HCV/HIV coinfected patients were retrospectively recruited in our Hospital from 2010 to 2011. Logistic regression analysis adjusting by [Age], [Sex], [HCV viral genotype], [HCV viral load], [HIV viral load], and [CD4 T cells levels] revealed the IL-28B rs12979860 (CT/TT) genotype as a protective factor against alanine aminotransferase (ALT) levels (>100 IU/L), aspartate aminotransferase (AST) levels (>75 IU/L), and AST-to-platelet ratio index (APRI) score for liver fibrosis (>1.5) [OR, (95% CI), p]: ALT [0.026 (0.001-0.576) 0.021]; AST [0.001 (0.000-0.297) 0.019]; APRI [0.031 (0.002-0.41) 0.008]. Stepwise regression analysis considering the same adjusting variables showed the same results. In consequence, the IL-28B rs12979860 (CT/TT) genotype, which is a marker of poor response to HCV treatment, could be mediating on the contrary a certain protective effect against the hepatic damage caused by this virus in patients coinfected by HIV.

Prevalencia de los marcadores de infección de los virus de las hepatitis en pacientes portadores del VIH en el sur de España / Prevalence of hepatitis virus infection markers in HIV-infected patients in Southern Spain

Objetivos Determinar en pacientes infectados por VIH: a) La prevalencia de infección activa por el virus de la hepatitis C (VHC) y el virus de la hepatitis B (VHB), así como de la exposición previa al virus de la hepatitis A (VHA), VHB y VHC. b) La proporción que han sido vacunados frente al VHA y/o VHB. c) La distribución genotípica del VHC y el porcentaje de pacientes que han iniciado tratamiento frente al VHC. Métodos Estudio prospectivo de corte transversal. Se incluyeron los pacientes infectados por VIH que acudieron a las consultas de enfermedades infecciosas de un hospital de Andalucía entre septiembre 2008 y febrero 2009.Resultados Se incluyeron 520 pacientes. Trescientos cincuenta y ocho (69%) enfermos presentaban anticuerpos del VHC positivo, mientras el 71% de ellos tenían ARN-VHC detectable. La distribución genotípica del VHC fue: 153 (62%) genotipo 1, 49 (20%) genotipo 3, y 45 (18%) genotipo 4. Ciento trece (36,5%) sujetos habían recibido tratamiento anti-VHC. La prevalencia de infección activa por VHB fue del 4,4%, mientras que la de exposición previa fue del 54,8%. Cuatrocientos treinta y siete (84%) enfermos presentaron anti-VHA positivo. El 25,6 y el 22,3% de los pacientes susceptibles habían sido vacunados frente al VHA y al VHB, respectivamente. Conclusiones La prevalencia actual de infección activa por VHC en los pacientes infectados por VIH sigue siendo elevada en nuestra área. La distribución genotípica del VHC no parece haber sufrido modificaciones notables. El número de pacientes susceptibles de ser vacunados frente al VHA y al VHB que reciben esta terapia preventiva es bajo (AU)

Objectives: To determine: (a) The prevalence of active infection by the hepatitis C virus (HCV) and hepatitis B virus (HBV) in HIV-infected patients, as well as previous exposure to hepatitis A virus (HAV), HBV and HCV. (b) The proportion of patients who have been vaccinated against HAV and/or HBV. (c) The HCV genotype distribution and the percentage of patients who have started treatment against HCV infection. Methods: All HIV-infected patients who attended the Infectious Diseases Unit of a tertiary care hospital in Southern Spain between September 2008 and February 2009 were included in a prospective crosssectional study Results: A total of 520 patients were included. Three hundred and flfty-eight (69%) patients had positive HCV antibody, while 71% of them showed detectable HCV-RNA. The HCV genotype distribution was: 153(62%) genotype 1, 49 (20%) genotype 3, and 45 (18%) genotype 4. One hundred and thirteen (36.5%) subjects had received treatment against HCV. The prevalence of active HBV infection was 4.4%, while the exposure to HBV was 54.8%. Four hundred and thirty-seven (84%) patients had positive markers of infection of HAV. Of the patients eligible to be vaccinated, 25.6% and 22.3% patients were vaccinated against HAV and HBV, respectively. Conclusions: The current prevalence of active HCV infection remains high in our area. There were no changes in the HCV genotype distribution. The number of patients with indication for HBV and HAV vaccination and receive these vaccines is low (AU)