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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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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. |
format | Online Article Text |
id | pubmed-7026412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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