TY - JOUR
T1 - Different modes of herpes simplex virus type 1 spread in brain and skin tissues
AU - Tsalenchuck, Yael
AU - Tzur, Tomer
AU - Steiner, Israel
AU - Panet, Amos
N1 - Funding Information:
This work was supported by a grant from the European Union (program number 6), the Clinigene Network of Excellence, and by The Israeli Academy of Sciences.
PY - 2014/2
Y1 - 2014/2
N2 - Herpes simplex virus type 1 (HSV-1) initially infects the skin and subsequently spreads to the nervous system. To investigate and compare HSV-1 mode of propagation in the two clinically relevant tissues, we have established ex vivo infection models, using native tissues of mouse and human skin, as well as mouse brain, maintained in organ cultures. HSV-1, which is naturally restricted to the human, infects and spreads in the mouse and human skin tissues in a similar fashion, thus validating the mouse model. The spread of HSV-1 in the skin was concentric to form typical plaques of limited size, predominantly of cytopathic cells. By contrast, HSV-1 spread in the brain tissue was directed along specific neuronal networks with no apparent cytopathic effect. Two additional differences were noted following infection of the skin and brain tissues. First, only a negligible amount of extracellular progeny virus was produced of the infected brain tissues, while substantial quantity of infectious progeny virus was released to the media of the infected skin. Second, antibodies against HSV-1, added following the infection, effectively restricted viral spread in the skin but have no effect on viral spread in the brain tissue. Taken together, these results reveal that HSV-1 spread within the brain tissue mostly by direct transfer from cell to cell, while in the skin the progeny extracellular virus predominates, thus facilitating the infection to new individuals.
AB - Herpes simplex virus type 1 (HSV-1) initially infects the skin and subsequently spreads to the nervous system. To investigate and compare HSV-1 mode of propagation in the two clinically relevant tissues, we have established ex vivo infection models, using native tissues of mouse and human skin, as well as mouse brain, maintained in organ cultures. HSV-1, which is naturally restricted to the human, infects and spreads in the mouse and human skin tissues in a similar fashion, thus validating the mouse model. The spread of HSV-1 in the skin was concentric to form typical plaques of limited size, predominantly of cytopathic cells. By contrast, HSV-1 spread in the brain tissue was directed along specific neuronal networks with no apparent cytopathic effect. Two additional differences were noted following infection of the skin and brain tissues. First, only a negligible amount of extracellular progeny virus was produced of the infected brain tissues, while substantial quantity of infectious progeny virus was released to the media of the infected skin. Second, antibodies against HSV-1, added following the infection, effectively restricted viral spread in the skin but have no effect on viral spread in the brain tissue. Taken together, these results reveal that HSV-1 spread within the brain tissue mostly by direct transfer from cell to cell, while in the skin the progeny extracellular virus predominates, thus facilitating the infection to new individuals.
KW - Brain
KW - HSV-1
KW - Skin
KW - Spread
UR - http://www.scopus.com/inward/record.url?scp=84896721458&partnerID=8YFLogxK
U2 - 10.1007/s13365-013-0224-4
DO - 10.1007/s13365-013-0224-4
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C2 - 24408306
AN - SCOPUS:84896721458
SN - 1355-0284
VL - 20
SP - 18
EP - 27
JO - Journal of NeuroVirology
JF - Journal of NeuroVirology
IS - 1
ER -