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      HIV-1 Unique Recombinant Forms Identified in Slovenia and Their Characterization by Near Full-Length Genome Sequencing

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          Abstract

          Surveillance of HIV circulating recombinant forms (CRFs) is important because HIV diversity can affect various aspects of HIV infection from prevention to diagnosis and patient management. A comprehensive collection of pol sequences obtained from individuals diagnosed with HIV-1 from 2000 to 2016 in Slovenia was subtyped to identify possible unique recombinant forms (URFs). Selected samples were subjected to near full-length genome (NFLG) sequencing and detailed recombination analyses. Discordant subtyping results were observed for 68/387 (17.6%) sequences and 20 sequences were identified as the most probable URFs and selected for NFLG characterization. Further, 11 NFLGs and two sequences of >7000 base pairs were obtained. Seven sequences were identified as “pure” subtypes or already characterized CRFs: subtype B ( n = 5), sub-subtype A6 ( n = 1), and CRF01_AE ( n = 1). The remaining six sequences were determined to be URFs; four displayed a single recombination event and two exhibited a complex recombination pattern involving several subtypes or CRFs. Finally, three HIV strains were recognized as having epidemic potential and could be further characterized as new CRFs. Our study shows that the identification of new CRFs is possible, even in countries where HIV diversity is considered limited, emphasizing the importance of the surveillance of HIV recombinant forms.

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          Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

          The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
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            Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.

            Treatment of infected patients with ABT-538, an inhibitor of the protease of human immunodeficiency virus type 1 (HIV-1), causes plasma HIV-1 levels to decrease exponentially (mean half-life, 2.1 +/- 0.4 days) and CD4 lymphocyte counts to rise substantially. Minimum estimates of HIV-1 production and clearance and of CD4 lymphocyte turnover indicate that replication of HIV-1 in vivo is continuous and highly productive, driving the rapid turnover of CD4 lymphocytes.
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              HIV-1 nomenclature proposal.

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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                03 January 2020
                January 2020
                : 12
                : 1
                : 63
                Affiliations
                Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia; maja.lunar@ 123456mf.uni-lj.si (M.M.L.); jana.mlakar@ 123456mf.uni-lj.si (J.M.); tomaz-mark.zorec@ 123456mf.uni-lj.si (T.M.Z.)
                Author notes
                [* ]Correspondence: mario.poljak@ 123456mf.uni-lj.si ; Tel.: +386-1-543-7453
                Author information
                https://orcid.org/0000-0001-8191-0994
                https://orcid.org/0000-0002-3216-7564
                Article
                viruses-12-00063
                10.3390/v12010063
                7019782
                31947872
                e664b4b1-fa04-47c2-afde-44aaed1dcce0
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 December 2019
                : 31 December 2019
                Categories
                Article

                Microbiology & Virology
                hiv-1,molecular epidemiology,subtype,unique recombinant form,near full-length genome,next-generation sequencing,surveillance

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