tetano
Editor, Senior Moderator
J Virol. 2014 Nov 26. pii: JVI.03306-14. [Epub ahead of print]
Influenza A virus uses intercellular connections to spread to neighboring cells.
Roberts KL1, Manicassamy B2, Lamb RA3.
Author information
Abstract
In the extracellular environment cell-free virions seek out na?ve host cells over long distances and between organisms. This is the primary mechanism of spread for most viruses. Here we provide evidence for an alternative pathway previously undescribed for Orthomyxoviruses where the spread of influenza A virus (IAV) infectious cores to neighboring cells can occur within intercellular connections. The formation of these connections requires actin dynamics and is enhanced by viral infection. Connected cells have contiguous membranes and the core infectious viral machinery (RNP and polymerase) were present inside the intercellular connections. A live cell movie of GFP-tagged NS1 of IAV shows viral protein moving from one cell to another through an intercellular connection. Movement of tagged protein was saltatory but overall traveled only in one direction. Infectious virus cores can move from one cell to another without budding and release of cell-free virions, as evidenced by finding that whereas a neuraminidase inhibitor alone did not inhibit the development of IAV microplaques, the presence of a neuraminidase inhibitor together with drugs inhibiting actin dynamics, or the microtubule stabilizer taxol precluded microplaque formation. Similar results were also observed with parainfluenza virus 5 (PIV5), a paramyxovirus, when neutralizing antibody was used to block spread by cell-free virions. Intercellular spread of infectious core particles was unaffected or enhanced in the presence of nocodazole for IAV but inhibited for PIV5. The intercellular connections have a core of filamentous actin, which hints toward transport of virus particles through the use of a myosin motor.
IMPORTANCE:
Here we describe a new method by which influenza A virus (IAV) spreads from cell to cell: IAV uses tunneling nanotubes. The formation of these connections requires actin dynamics and is enhanced by viral infection and the absence of microtubules. Connected cells appeared to have contiguous membranes and the core infectious viral machinery (RNP and polymerase) were present inside the intercellular connections. Infectious virus cores can move from one cell to another without budding and release of cell-free virions. Similar results were also observed with parainfluenza virus 5 (PIV5).
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25428869
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25428869
Influenza A virus uses intercellular connections to spread to neighboring cells.
Roberts KL1, Manicassamy B2, Lamb RA3.
Author information
Abstract
In the extracellular environment cell-free virions seek out na?ve host cells over long distances and between organisms. This is the primary mechanism of spread for most viruses. Here we provide evidence for an alternative pathway previously undescribed for Orthomyxoviruses where the spread of influenza A virus (IAV) infectious cores to neighboring cells can occur within intercellular connections. The formation of these connections requires actin dynamics and is enhanced by viral infection. Connected cells have contiguous membranes and the core infectious viral machinery (RNP and polymerase) were present inside the intercellular connections. A live cell movie of GFP-tagged NS1 of IAV shows viral protein moving from one cell to another through an intercellular connection. Movement of tagged protein was saltatory but overall traveled only in one direction. Infectious virus cores can move from one cell to another without budding and release of cell-free virions, as evidenced by finding that whereas a neuraminidase inhibitor alone did not inhibit the development of IAV microplaques, the presence of a neuraminidase inhibitor together with drugs inhibiting actin dynamics, or the microtubule stabilizer taxol precluded microplaque formation. Similar results were also observed with parainfluenza virus 5 (PIV5), a paramyxovirus, when neutralizing antibody was used to block spread by cell-free virions. Intercellular spread of infectious core particles was unaffected or enhanced in the presence of nocodazole for IAV but inhibited for PIV5. The intercellular connections have a core of filamentous actin, which hints toward transport of virus particles through the use of a myosin motor.
IMPORTANCE:
Here we describe a new method by which influenza A virus (IAV) spreads from cell to cell: IAV uses tunneling nanotubes. The formation of these connections requires actin dynamics and is enhanced by viral infection and the absence of microtubules. Connected cells appeared to have contiguous membranes and the core infectious viral machinery (RNP and polymerase) were present inside the intercellular connections. Infectious virus cores can move from one cell to another without budding and release of cell-free virions. Similar results were also observed with parainfluenza virus 5 (PIV5).
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25428869
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25428869