Differential prevalence of the HLA-C −35 CC genotype among viremic long term non-progressor and elite controller HIV+ individuals

Immunobiology ◽  
2012 ◽  
Vol 217 (9) ◽  
pp. 889-894 ◽  
Author(s):  
Ester Ballana ◽  
Alba Ruiz-de Andres ◽  
Beatriz Mothe ◽  
Eva Ramirez de Arellano ◽  
Francisco Aguilar ◽  
...  
Keyword(s):  
mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Concepción Casado ◽  
Sara Marrero-Hernández ◽  
Daniel Márquez-Arce ◽  
María Pernas ◽  
Sílvia Marfil ◽  
...  

ABSTRACTA small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs), display permanent control of viral replication and lack of clinical progression. This control is the result of a complex interaction of host, immune, and viral factors. We identified, by phylogenetic analysis, a cluster of LTNP-ECs infected with very similar low-replication HIV-1 viruses, suggesting the contribution of common viral features to the clinical LTNP-EC phenotype. HIV-1 envelope (Env) glycoprotein mediates signaling and promotes HIV-1 fusion, entry, and infection, being a key factor of viral fitnessin vitro, cytopathicity, and infection progressionin vivo. Therefore, we isolated full-lengthenvgenes from viruses of these patients and from chronically infected control individuals. Functional characterization of the initial events of the viral infection showed that Envs from the LTNP-ECs were ineffective in the binding to CD4 and in the key triggering of actin/tubulin-cytoskeleton modifications compared to Envs from chronic patients. The viral properties of the cluster viruses result in a defective viral fusion, entry, and infection, and these properties were inherited by every virus of the cluster. Therefore, inefficient HIV-1 Env functions and signaling defects may contribute to the low viral replication capacity and transmissibility of the cluster viruses, suggesting a direct role in the LTNP-EC phenotype of these individuals. These results highlight the important role of viral characteristics in the LTNP-EC clinical phenotype. These Env viral properties were common to all the cluster viruses and thus support the heritability of the viral characteristics.IMPORTANCEHIV-1 long-term nonprogressor elite controller patients, due to their permanent control of viral replication, have been the object of numerous studies to identify the factors responsible for this clinical phenotype. In this work, we analyzed the viral characteristics of the envelopes of viruses from a phylogenetic cluster of LTNP-EC patients. These envelopes showed ineffective binding to CD4 and the subsequent signaling activity to modify actin/tubulin cytoskeletons, which result in low fusion and deficient entry and infection capacities. These Env viral characteristics could explain the nonprogressor clinical phenotype of these patients. In addition, these inefficientenvviral properties were present in all viruses of the cluster, supporting the heritability of the viral phenotype.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Francisco Díez-Fuertes ◽  
Humberto Erick De La Torre-Tarazona ◽  
Esther Calonge ◽  
Maria Pernas ◽  
María del Mar Alonso-Socas ◽  
...  

Abstract The elite controller (EC)-long term non-progressor (LTNP) phenotype represent a spontaneous and advantageous model of HIV-1 control in the absence of therapy. The transcriptome of peripheral blood mononuclear cells (PBMCs) collected from EC-LTNPs was sequenced by RNA-Seq and compared with the transcriptomes from other phenotypes of disease progression. The transcript abundance estimation combined with the use of supervised classification algorithms allowed the selection of 20 genes and pseudogenes, mainly involved in interferon-regulated antiviral mechanisms and cell machineries of transcription and translation, as the best predictive genes of disease progression. Differential expression analyses between phenotypes showed an altered calcium homeostasis in EC-LTNPs evidenced by the upregulation of several membrane receptors implicated in calcium-signaling cascades and intracellular calcium-mobilization and by the overrepresentation of NFAT1/Elk-1-binding sites in the promoters of the genes differentially expressed in these individuals. A coordinated upregulation of host genes associated with HIV-1 reverse transcription and viral transcription was also observed in EC-LTNPs –i.e. p21/CDKN1A, TNF, IER3 and GADD45B. We also found an upregulation of ANKRD54 in EC-LTNPs and viremic LTNPs in comparison with typical progressors and a clear alteration of type-I interferon signaling as a consequence of viremia in typical progressors before and after receiving antiretroviral therapy.


2008 ◽  
Vol 47 (11) ◽  
pp. e86-e89 ◽  
Author(s):  
Andrea Rachinger ◽  
Marjon Navis ◽  
Sander van Assen ◽  
Paul H. P. Groeneveld ◽  
Hanneke Schuitemaker
Keyword(s):  

2019 ◽  
Vol 42 ◽  
Author(s):  
John P. A. Ioannidis

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.


2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.


1999 ◽  
Vol 173 ◽  
pp. 189-192
Author(s):  
J. Tichá ◽  
M. Tichý ◽  
Z. Moravec

AbstractA long-term photographic search programme for minor planets was begun at the Kleť Observatory at the end of seventies using a 0.63-m Maksutov telescope, but with insufficient respect for long-arc follow-up astrometry. More than two thousand provisional designations were given to new Kleť discoveries. Since 1993 targeted follow-up astrometry of Kleť candidates has been performed with a 0.57-m reflector equipped with a CCD camera, and reliable orbits for many previous Kleť discoveries have been determined. The photographic programme results in more than 350 numbered minor planets credited to Kleť, one of the world's most prolific discovery sites. Nearly 50 per cent of them were numbered as a consequence of CCD follow-up observations since 1994.This brief summary describes the results of this Kleť photographic minor planet survey between 1977 and 1996. The majority of the Kleť photographic discoveries are main belt asteroids, but two Amor type asteroids and one Trojan have been found.


1994 ◽  
Vol 144 ◽  
pp. 29-33
Author(s):  
P. Ambrož

AbstractThe large-scale coronal structures observed during the sporadically visible solar eclipses were compared with the numerically extrapolated field-line structures of coronal magnetic field. A characteristic relationship between the observed structures of coronal plasma and the magnetic field line configurations was determined. The long-term evolution of large scale coronal structures inferred from photospheric magnetic observations in the course of 11- and 22-year solar cycles is described.Some known parameters, such as the source surface radius, or coronal rotation rate are discussed and actually interpreted. A relation between the large-scale photospheric magnetic field evolution and the coronal structure rearrangement is demonstrated.


2000 ◽  
Vol 179 ◽  
pp. 201-204
Author(s):  
Vojtech Rušin ◽  
Milan Minarovjech ◽  
Milan Rybanský

AbstractLong-term cyclic variations in the distribution of prominences and intensities of green (530.3 nm) and red (637.4 nm) coronal emission lines over solar cycles 18–23 are presented. Polar prominence branches will reach the poles at different epochs in cycle 23: the north branch at the beginning in 2002 and the south branch a year later (2003), respectively. The local maxima of intensities in the green line show both poleward- and equatorward-migrating branches. The poleward branches will reach the poles around cycle maxima like prominences, while the equatorward branches show a duration of 18 years and will end in cycle minima (2007). The red corona shows mostly equatorward branches. The possibility that these branches begin to develop at high latitudes in the preceding cycles cannot be excluded.


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