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In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha

Type I interferons, particularly interferon-alpha (IFN-α), play a vital role in the host's anti-viral defenses by interfering with viral replication. However, the virus rapidly evolves to exploit the IFN-α response for its replication, spread, and pathogenic function. In this study, we attempte...

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Autores principales: Ashok kumar, Manickam, Sonawane, Aanand, Sperk, Maike, Tripathy, Srikanth P., Neogi, Ujjwal, Hanna, Luke Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026412/
https://www.ncbi.nlm.nih.gov/pubmed/32066770
http://dx.doi.org/10.1038/s41598-020-59596-x
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author Ashok kumar, Manickam
Sonawane, Aanand
Sperk, Maike
Tripathy, Srikanth P.
Neogi, Ujjwal
Hanna, Luke Elizabeth
author_facet Ashok kumar, Manickam
Sonawane, Aanand
Sperk, Maike
Tripathy, Srikanth P.
Neogi, Ujjwal
Hanna, Luke Elizabeth
author_sort Ashok kumar, Manickam
collection PubMed
description Type I interferons, particularly interferon-alpha (IFN-α), play a vital role in the host's anti-viral defenses by interfering with viral replication. However, the virus rapidly evolves to exploit the IFN-α response for its replication, spread, and pathogenic function. In this study, we attempted to determine IFN-α susceptibility and productivity of infectious transmitted/founder (TF) (n = 8) and non-transmitted (NT) viruses (n = 8) derived from HIV-1 infected infants. Independent experiments were carried out to determine IFN-α resistance, replication fitness, and viral productivity in CD4(+) T cells over a short period. In vitro studies showed that TF viruses were resistant to IFN-α during the very near moment of transmission, but in the subsequent time points, they became susceptible to IFN-α. We did not observe much difference in replicative fitness of the TF viruses in cultures treated with and without IFN-α, but the difference was significant in the case of NT viruses obtained from the same individual. Despite increased susceptibility to IFN-α, NT viruses produced more viral particles than TF viruses. Similar results were also obtained in cultures treated with maraviroc (MVC). The study identified unique characteristics of TF viruses thus prompting further investigation into virus-host interaction occurring during the early stages of HIV infection.
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spelling pubmed-70264122020-02-26 In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha Ashok kumar, Manickam Sonawane, Aanand Sperk, Maike Tripathy, Srikanth P. Neogi, Ujjwal Hanna, Luke Elizabeth Sci Rep Article Type I interferons, particularly interferon-alpha (IFN-α), play a vital role in the host's anti-viral defenses by interfering with viral replication. However, the virus rapidly evolves to exploit the IFN-α response for its replication, spread, and pathogenic function. In this study, we attempted to determine IFN-α susceptibility and productivity of infectious transmitted/founder (TF) (n = 8) and non-transmitted (NT) viruses (n = 8) derived from HIV-1 infected infants. Independent experiments were carried out to determine IFN-α resistance, replication fitness, and viral productivity in CD4(+) T cells over a short period. In vitro studies showed that TF viruses were resistant to IFN-α during the very near moment of transmission, but in the subsequent time points, they became susceptible to IFN-α. We did not observe much difference in replicative fitness of the TF viruses in cultures treated with and without IFN-α, but the difference was significant in the case of NT viruses obtained from the same individual. Despite increased susceptibility to IFN-α, NT viruses produced more viral particles than TF viruses. Similar results were also obtained in cultures treated with maraviroc (MVC). The study identified unique characteristics of TF viruses thus prompting further investigation into virus-host interaction occurring during the early stages of HIV infection. Nature Publishing Group UK 2020-02-17 /pmc/articles/PMC7026412/ /pubmed/32066770 http://dx.doi.org/10.1038/s41598-020-59596-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ashok kumar, Manickam
Sonawane, Aanand
Sperk, Maike
Tripathy, Srikanth P.
Neogi, Ujjwal
Hanna, Luke Elizabeth
In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha
title In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha
title_full In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha
title_fullStr In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha
title_full_unstemmed In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha
title_short In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha
title_sort in vitro replicative fitness of early transmitted founder hiv-1 variants and sensitivity to interferon alpha
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026412/
https://www.ncbi.nlm.nih.gov/pubmed/32066770
http://dx.doi.org/10.1038/s41598-020-59596-x
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