CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells
Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we gen...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Society for General Microbiology
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885024/ https://www.ncbi.nlm.nih.gov/pubmed/19088272 http://dx.doi.org/10.1099/vir.0.006700-0 |
_version_ | 1782182342658359296 |
---|---|
author | Witteveldt, Jeroen Evans, Matthew J. Bitzegeio, Julia Koutsoudakis, George Owsianka, Ania M. Angus, Allan G. N. Keck, Zhen-Yong Foung, Steven K. H. Pietschmann, Thomas Rice, Charles M. Patel, Arvind H. |
author_facet | Witteveldt, Jeroen Evans, Matthew J. Bitzegeio, Julia Koutsoudakis, George Owsianka, Ania M. Angus, Allan G. N. Keck, Zhen-Yong Foung, Steven K. H. Pietschmann, Thomas Rice, Charles M. Patel, Arvind H. |
author_sort | Witteveldt, Jeroen |
collection | PubMed |
description | Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1(ΔE1E2)-transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1(W529A) was unaffected by the presence of neutralizing antibodies that inhibit E2–CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission. |
format | Text |
id | pubmed-2885024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Society for General Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-28850242010-06-21 CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells Witteveldt, Jeroen Evans, Matthew J. Bitzegeio, Julia Koutsoudakis, George Owsianka, Ania M. Angus, Allan G. N. Keck, Zhen-Yong Foung, Steven K. H. Pietschmann, Thomas Rice, Charles M. Patel, Arvind H. J Gen Virol Jgv Direct Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1(ΔE1E2)-transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1(W529A) was unaffected by the presence of neutralizing antibodies that inhibit E2–CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission. Society for General Microbiology 2009-01 /pmc/articles/PMC2885024/ /pubmed/19088272 http://dx.doi.org/10.1099/vir.0.006700-0 Text en Copyright © 2009, SGM http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Jgv Direct Witteveldt, Jeroen Evans, Matthew J. Bitzegeio, Julia Koutsoudakis, George Owsianka, Ania M. Angus, Allan G. N. Keck, Zhen-Yong Foung, Steven K. H. Pietschmann, Thomas Rice, Charles M. Patel, Arvind H. CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells |
title | CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells |
title_full | CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells |
title_fullStr | CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells |
title_full_unstemmed | CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells |
title_short | CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells |
title_sort | cd81 is dispensable for hepatitis c virus cell-to-cell transmission in hepatoma cells |
topic | Jgv Direct |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885024/ https://www.ncbi.nlm.nih.gov/pubmed/19088272 http://dx.doi.org/10.1099/vir.0.006700-0 |
work_keys_str_mv | AT witteveldtjeroen cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT evansmatthewj cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT bitzegeiojulia cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT koutsoudakisgeorge cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT owsiankaaniam cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT angusallangn cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT keckzhenyong cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT foungstevenkh cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT pietschmannthomas cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT ricecharlesm cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells AT patelarvindh cd81isdispensableforhepatitiscviruscelltocelltransmissioninhepatomacells |