The HIV pandemic is caused by viruses of type 1 group M (HIV-M). Beside the majority of these viruses, there are many divergent variants, leading to the definition of HIV-2 and group N, O and P in HIV-1. HIV-1 groups are the result of independent cross-species of viruses from chim- panzees and gorillas living in Western Central Africa. These simian origins and the necessary adaptation to the human species are the sources of genomic characteristics, phylogenetic and viral properties, specific to each group. The natural history of the infections associated to these variants nevertheless seems similar to that of HIV-M, with a high viral replication in vivo associated with immunosuppression. These non-M variants all have been described for the first time in patients of Cameroonian origin. The Western Central Africa is the epicenter of the epidemics of non-M variants, and the diffusion outside this area is anecdotal, except in France. In Cameroon, the origin of all groups cur- rently described, HIV-O infections account for 1% of HIV infections, while only 15 cases of HIV-N infections and two HIV-P infections have been repor- ted to date. If the important genetic diversity of these variants requires the use of specific tools for serological identification and molecular characterization, diagnosis and virological monitoring of these infections now appear possible with current commercial kits; however, very little data are available on the response to antiretroviral therapy and no recommendations are defined in case of failure. Despite improved knowledge on these rare variants, many fascinating questions persist about their origin, genetic evolution and reasons for their low epidemiological spread. Their discovery, and the description of many simian viruses, demonstrates a dynamic transmission to humans, making it likely that other variants may exist; we should therefore pursue a careful surveillance, especially when faced to discrepancy between screening and therapeutic management of HIV infections.
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http://dx.doi.org/10.1684/vir.2011.15884 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFBackground: Senile dementia (SD) is a deteriorative organic brain disorder and it comprises Alzheimer's disease (AD) as a major variant. SD is shown impairment of mental capacities whereas AD is degeneration of neurons. According to World Health Organization (WHO) report; more than 55 million peoples have dementia and it is raising 10 million new cases every year.
View Article and Find Full Text PDFBackground: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China;, Beijing, China.
Background: Individuals with type 2 diabetes mellitus (T2DM) face an increased risk of dementia. Recent discoveries indicate that SGLT2 inhibitors, a newer class of anti-diabetic medication, exhibit beneficial metabolic effects beyond glucose control, offering a potential avenue for mitigating the risk of Alzheimer's disease (AD). However, limited evidence exists regarding whether the use of SGLT2 inhibitors effectively reduces the risk of AD.
View Article and Find Full Text PDFBackground: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
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