Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain undetectable viral loads without antiretroviral therapy. The mechanism of control remains unclear, but the HLA-B75ء allele is overrepresented in cohorts of these patients. However, many HLA-B75ء patients develop progressive disease, and some studies have suggested that infection with defective viruses may be the cause of the lack of high levels of virus replication and disease progression in ES. We therefore performed a comprehensive comparative in vivo and in vitro characterization of viruses isolated from well-defined ES. For this purpose, we first performed full-genome sequence analysis and in vitro fitness assays on replication-competent isolates from HLA-B75ء ES and HLA-B75ء chronic progressors (CPs). Under our experimental conditions, we found that isolates from ES and CPs can replicate in vitro. However, since inherently these assays involve the use of unnaturally in vitro-activated cells, we also investigated the replication competence and pathogenic potential of these HIV isolates in vivo using humanized BLT mice. The results from these analyses demonstrate that virus isolates from ES are fully replication competent in vivo and can induce peripheral and systemic CD4 T cell depletion. These results provide the first direct in vivo evidence that viral fitness does not likely determine clinical outcome in HLA-B75ء patients and that elite suppressors can control replication-competent, fully pathogenic viruses. A better understanding of the immunological bases of viral suppression in ES will serve to inform novel approaches to preventive and therapeutic HIV vaccine design.
IMPORTANCEElite suppressors are HIV-1-infected patients who have undetectable levels of viremia despite not being on antiviral drugs. One of the most fundamental questions about this phenomenon involves the mechanism of control. To address this question, we isolated virus from elite suppressors and from HIV-1-infected patients who have the usual progressive disease course. We compared how well the isolates from the two groups of patients replicated in culture and in humanized mice. Our results suggest that elite suppressors are capable of controlling HIV-1 due to the possession of unique host factors rather than infection with defective virus.
Developing eco-friendly, robust,
and multifunctional conductive
polymer composites is highly desirable for using as flexible wearable
electric elements and meeting the requirements of a sustainable society.
Herein, we construct multifunctional cellulose/MWCNT composite films
with a superhigh Joule heating performance, outstanding electromagnetic
interference (EMI)-shielding efficiency, high electrical conductivity,
good mechanical properties, excellent thermostability, and adequate
water resistance. The resultant cellulose/MWCNT composite films possess
a special segregated MWCNT conductive network structure by using a
simple paper-making process and a subsequent in situ welding process
with an ionic liquid as the solvent of cellulose. Their EMI-shielding
effectiveness reaches 49.2 dB with a thickness of 0.3 mm, their electrical
conductivity reaches 1901 S/m, their tensile strength reaches 110
MPa, and their initial decomposition temperature is higher than 300
°C. In particular, they show a superhigh Joule heating performance
at a low driving voltage. When the driving voltage is as low as 2
V, the temperature of the cellulose/MWCNT composite rapidly increases
to 166 °C, which is dramatically higher than those of the previously
reported polymer composite heaters. Cellulose/MWCNT composite films
with such an outstanding combination performance can be used as multifunctional
flexible conductive elements for the fabrication of a deicing device,
a portable heat sealer, and an EMI-shielding device.
Macaque species serve as important animal models of human infection and immunity. To more fully scrutinize their potential in both the analysis of disease pathogenesis and vaccine development, it is necessary to characterize the Major Histocompatibility Complex (MHC) class I loci of Macaca mulatta (Mamu), Macaca nemestrina (Mane), and Macaca fascicularis (Mafa) at the genomic level. The oligomorphic Mamu-A2*05/Mane-A2*05 (previously known as Mane-A*06) family of macaque MHC-A alleles has recently been shown to be present at high frequency in both Indian rhesus and pig-tailed macaque populations. Using a locus-specific amplification and direct DNA typing methodology, we have additionally found that the locus encoding this family is very prevalent (75%) among a sampling of 182 Chinese rhesus macaques and has a high prevalence (80%) within a larger, independent cohort of 309 pig-tailed macaques. Interestingly, among the Chinese rhesus macaques, only 6 alleles previously identified in Indian-origin animals were observed, while 3 recently identified in Chinese-origin animals and 25 new alleles were characterized. Among the pig-tailed macaques, we observed one previously known (Mane-A*06) and 19 new alleles. Examination of the orthologous locus in a preliminary sampling of 30 cynomolgus macaques revealed an even higher presence (87%) of Mafa-A2*05 family alleles, with 5 previously identified and 15 new ones characterized. The continued discovery of novel alleles and thus further diversity within the Mamu-A2*05/Mane-A2*05/Mafa-A2*05 family indicates that this MHC-A locus, although highly conserved across the three species of macaques, has remained a dynamic entity during evolution.
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