Maturation and release of human immunodeficiency virus type 1 (HIV-1) is targeted at the pseudopod of infected mononuclear cells. However, the intracellular mechanism or targeting signals leading to this polarized viral maturation are yet to be identified. We have recently demonstrated the presence of a functional YXXL motif for specific targeting of HIV-1 virions to the basolateral membrane surface in polarized epithelial Madin-Darby canine kidney cells (MDCK). Site-directed mutagenesis was used to demonstrate that the membrane-proximal tyrosine in the intracytoplasmic tail of the HIV-1 transmembrane glycoprotein (gp41) is an essential component of this signal. In the present study, immunolocalization of viral budding allowed us to establish that this tyrosine-based signal is involved in determining the exact site of viral release at the surface of infected mononuclear cells. Substitution of the critical tyrosine residue was also shown to increase the amount of envelope glycoprotein at the cell surface, supporting previous suggestions that the tyrosine-based motif can promote endocytosis. Although alteration of the dual polarization-endocytosis motif did not affect the infectivity of cell-free virus, it could play a key role in cell-to-cell viral transmission. Accordingly, chronically infected lymphocytes showed a reduced ability to transmit the mutant virus to a cocultivated cell line. Overall, our data indicate that the YXXL targeting motif of HIV is active in various cell types and could play an important role in viral propagation; this may constitute an alternative target for HIV therapeutics and vaccine development.
HIV infection has a tremendous impact on the immune system's proper functioning. The mucosaassociated lymphoid tissue (MALT) is significantly disarrayed during HIV infection.Compositional changes in the gut microbiota might contribute to the mucosal barrier disruption, and consequently to microbial translocation. We performed an observational, cross-sectional study aimed at evaluating changes in the fecal microbiota of HIV-infected individuals from Colombia. We analyzed the fecal microbiota of 37 individuals via 16S rRNA gene sequencing; 25 HIV-infected patients and 12 control (non-infected) individuals, which were similar in body mass index, age, gender balance and socioeconomic status. To the best of our knowledge, no such studies have been conducted in Latin American countries. Given its compositional nature, microbiota data were normalized and transformed using Aitchison's Centered Log-Ratio. Overall, a change in the network structure in HIV-infected patients was revealed by using the SPIEC-EASI MB tool. Genera such as Blautia, Dorea, Yersinia, Escherichia-Shigella complex, Staphylococcus, and Bacteroides were highly relevant in HIV-infected individuals. Differential abundance analysis by both sparse Partial Least Square-Discriminant Analysis and Random Forest identified a greater abundance of Lachnospiraceae-OTU69, Blautia, Dorea, Roseburia, and Erysipelotrichaceae in HIV-infected individuals. We show here, for the first time, a predominantly Lachnospiraceae-based signature in HIV-infected individuals.The health complications arising from HIV infection associated to developing acquired immunodeficiency syndrome impose a heavy physical and psychological toll on people 1 . Approximately 78 million people have been diagnosed with HIV, of whom ~35 million people have died. In 2015 alone, there were 36.7 million people living with HIV 1,2 . Among the 4 HIV groups, M is the most widely distributed group and is comprised of nine subtypes. Subtype C is responsible for about one-half of all global infections, while subtype B, the prevalent virus in Colombia, is the most widespread 3,4 . A mucosal barrier integrated by the intestinal epithelium and the underlying immune system favors tolerance towards bacteria present in the intestine lumen [5][6][7][8][9] . Commensal bacteria of the intestinal microbiota also contribute to the mucosal barrier by competing for space and resources with potentially pathobiontic bacteria 10 . HIV
Objectives: Treatment failure in patients receiving antiretroviral therapy against human immunodeficiency virus (HIV) is always a concern. The major aim of the present work was to examine the correlates associated with treatment failure in patients living in the Colombian Caribbean city of Barranquilla, an aspect that was poorly studied in this region. Methods: Treatment failure was evaluated in a cross-sectional study from virological, immunological and clinical standpoints. Results: It was established that 29.5% of patients under highly active antiretroviral therapy (HAART) could be considered in treatment failure. Among those, virological failure was most frequent (20.9%), followed by immunological- (14.0%) and clinical failure (4.7%). In patients showing lack of adherence to the treatment, the likelihood of suffering from treatment- and virogical-failure were respectively increased by 6.67-fold and 12.19-fold, compared with patients showing good adherence. Although there was no statistically significant association, treatment failure tended to be more frequent in young adults and in patients with low income or low level of education. When antiretroviral therapies (ART) regimens were compared, there was no apparent difference in treatment failure between regimens based on non-nucleoside reverse transcriptase inhibitors and those based on protease inhibitors. This is very important in the context of recent ART strategies, such as early-initiated ART, aimed at achieving long-term infection control. Conclusions: The current study confirms the importance of treatment adherence to avoid treatment failure and further highlights the importance of educating HIV-infected patients in all parts of the world, especially those individuals with a lower socio-economic status.
To characterize human immunodeficiency virus (HIV-1) strains circulating in the Northern region of Colombia in South America, sequences of the viral envelope C2V3C3 region were obtained from patients with different high-risk practices. Close to 60% of the sequences were predicted to belong to macrophage-tropic viruses, according to the positions of acidic amino acids and putative N-linked glycosylation sites. This is in agreement with the fact that most of the patients were recently diagnosed individuals. Phylogenic analysis then allowed assignment of all 35 samples to subtype B viruses. This same subtype was found in previous studies carried out in other Colombian regions. This study thus expands previous analyses with previously missing data from the Northern region of the country. The number and the length of the sequences examined also help to provide a clearer picture of the prevailing situation of the present HIV epidemics in this country.
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