HLA-Bw4 Homozygosity Is Associated with an Impaired CD4 T Cell Recovery after Initiation of Antiretroviral Therapy

We assessed the influence of human leukocyte antigen (HLA) alleles HLA-Bw4 and HLA-Bw6 on CD4 T cell recovery after starting successful combination antiretroviral therapy in 265 individuals. The median gains in the CD4 T cell count after 4 years were 258 cells/µL for HLA-Bw4 homozygotes, 321 cells/µL for HLA-Bw4/Bw6 heterozygotes, and 363 cells/µL for HLA-Bw6 homozygotes (P=.01, compared with HLA-Bw4 homozygotes). HLA-Bw4 homozygosity appears to predict an impaired CD4 T cell recovery after initiation of combination antiretroviral therap

Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels. AIMS: To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication. METHODS: T cell responses were evaluated longitudinally in 80 HIV/HCV coinfected individuals by ex vivo interferon-gamma-ELISpot responses to HCV core peptides, that predominantly stimulate CD4(+) T cells. HCV RNA levels were assessed by real-time PCR in 114 individuals. RESULTS: The proportion of individuals with detectable T cell responses to HCV core peptides was 19% before starting cART, 24% in the first year on cART and increased significantly to 45% and 49% after 33 and 70 months on cART (p=0.001). HCV-specific immune responses increased in individuals with chronic (+31%) and spontaneously cleared HCV infection (+30%). Median HCV RNA levels before starting cART were 6.5 log(10) IU/ml. During long-term cART, median HCV-RNA levels slightly decreased compared to pre-cART levels (-0.3 log10 IU/ml, p=0.02). CONCLUSIONS: Successful cART is associated with increasing cellular immune responses to HCV core peptides and with a slight long-term decrease in HCV RNA levels. These findings are in line with the favourable clinical effects of cART on the natural history of hepatitis C and with the current recommendation to start cART earlier in HCV/HIV coinfected individuals

Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity

Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design

Differential expression levels of activating and inhibitory receptors on NK cell subsets: Relevance to NK cell function

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Differential gene expression profiling of NK cells

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Genetic Variation of Host Immune Response Genes and Their Effect on Hepatitis C Infection and Treatment Outcome

Effective control of pathogens is typically achieved by the timely interplay between the innate and adaptive immune response of an individual..

Alois Riegl’s “Baroque” in the light of selected passages in his unpublished manuscripts

This article deals with aspects of Alois Riegl’s investigation of Baroque art in light of selected passages of his still unpublished manuscripts. The analysis of this voluminous corpus, in comparison with Riegl’s posthumous publications on the “origins” of Baroque art, reveals not only a much more comprehensive study of Baroque art, but also a far more complex idea of “Baroque”. The purpose of the article is to advance knowledge about Riegl’s actual contribution to Baroque studies. Particular attention will be paid to both core concepts of Riegl’s analysis of Baroque art and his methodological approach, by highlighting reference models as well as divergences from contemporary research