Properties and Functions of Feline Immunodeficiency Virus Gag Domains in Virion Assembly and Budding
VIRUSES-BASEL
Authors: Gonzalez, Silvia A.; Affranchino, Jose L.
Abstract
Feline immunodeficiency virus (FIV) is an important cat pathogen worldwide whose biological and pathophysiological properties resemble those of human immunodeficiency virus type 1 (HIV-1). Therefore, the study of FIV not only benefits its natural host but is also useful for the development of antiviral strategies directed against HIV-1 infections in humans. FIV assembly results from the multimerization of a single but complex viral polypeptide, the Gag precursor. In this review, we will first give an overview of the current knowledge of the proteins encoded by the FIV pol, env, rev, vif, and orf-A genes, and then we will describe and discuss in detail the critical roles that each of the FIV Gag domains plays in virion morphogenesis. Since retroviral assembly is an attractive target for therapeutic interventions, gaining a better understanding of this process is highly desirable.
Prevalence and clinical impacts of HIV-1 intersubtype recombinants in Uganda revealed by near-full-genome population and deep sequencing approaches
AIDS
Authors: Lee, Guinevere Q.; Bangsberg, David R.; Mo, Theresa; Lachowski, Chris; Brumme, Chanson J.; Zhang, Wendy; Lima, Viviane D.; Boum, Yap, II; Mwebesa, Bosco Bwana; Muzoora, Conrad; Andia, Iren; Mbalibulha, Yona; Kembabazi, Annet; Carroll, Ryan; Siedner, Mark J.; Haberer, Jessica E.; Mocello, A. Rain; Kigozi, Simone H.; Hunt, Peter W.; Martin, Jeffrey N.; Harrigan, P. Richard
Abstract
Objectives: HIV-1 subtypes A1 and D cocirculate in a rural community in Mbarara, Uganda. This study examines HIV-1 intersubtype recombination in this community under a full-genome sequencing context. We aim to estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with intersubtype recombinants. Methods: Near-full-genome HIV-1 Sanger sequence data were collected from plasma samples of 504 treatment-naive individuals, who then received protease inhibitor or nonnucleoside reverse transcriptase inhibitor-containing regimens and were monitored for up to 7.5 years. Subtypes were inferred by Los Alamos Recombinant Identification Program (RIP) 3.0 and compared with Sanger/REGA and MiSeq/RIP. 'Nonrecombinants' and 'recombinants' infections were compared in terms of pretherapy viral load, CD4(+) cell count, posttherapy time to virologic suppression, virologic rebound, first CD4(+) rise above baseline and sustained CD4(+) recovery. Results: Prevalence of intersubtype recombinants varied depending on the genomic region examined: gag (15%), prrt (11%), int (8%), vif (10%), vpr (2%), vpu (9%), GP120 (8%), GP41 (18%), and nef (4%). Of the 200 patients with near-full-genome data, prevalence of intersubtype recombination was 46%; the most frequently observed recombinant was A1-D (25%). Sanger/REGA and MiSeq/RIP yielded generally consistent results. Phylogenetic tree revealed most recombinants did not share common ancestors. No temporal trend was observed (all P >0.1). Subsequent subtype switches were detected in 27 of 143 (19%) study participants with follow-up sequences. Nonrecombinant versus recombinants infections were not significantly different in any pre nor posttherapy clinical correlates examined (all P > 0.2). Conclusion: Intersubtype recombination was highly prevalent (46%) in Uganda if the entire HIV genome was considered, but was neither associated with clinical correlates nor therapy outcomes. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.