TY - JOUR
T1 - Differential in vitro infection of neural cells by astroviruses
AU - Janowski, Andrew B.
AU - Klein, Robyn S.
AU - Wang, David
N1 - Funding Information:
A.B.J. is supported in part by the NIH under the grant K08 AI132745. D.W. is supported in part by NIH grant R21 NS101371. The content is solely our responsibility and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 Janowski et al.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Recent advances in unbiased pathogen discovery have implicated astroviruses as pathogens of the central nervous system (CNS) of mammals, including humans. However, the capacity of astroviruses to be cultured in CNS-derived cells in vitro has not been reported to date. Both astrovirus VA1/HMO-C (VA1; mamastrovirus 9) and classic human astrovirus 4 (HAstV4; mamastrovirus 1) have been previously detected from cases of human encephalitis. We tested the ability of primary human neurons, primary human astrocytes, and other immortalized human nervous system cell lines (SK-N-SH, U87 MG, and SW-1088) to support infection and replication of these two astrovirus genotypes. Primary astrocytes and SK-N-SH cells supported the full viral life cycle of VA1 with a >100-fold increase in viral RNA levels during a multistep growth curve, detection of viral capsid, and a >100-fold increase in viral titer. Primary astrocytes were permissive with respect to HAstV4 infection and replication but did not yield infectious virus, suggesting abortive infection. Similarly, abortive infection of VA1 was observed in SW-1088 and U87 MG cells. Elevated expression of the chemokine CXCL10 was detected in VA1-infected primary astrocytes and SK-N-SH cells, suggesting that VA1 infection can induce a proinflammatory host response. These findings establish an in vitro cell culture model that is essential for investigation of the basic biology of astroviruses and their neuropathogenic potential.
AB - Recent advances in unbiased pathogen discovery have implicated astroviruses as pathogens of the central nervous system (CNS) of mammals, including humans. However, the capacity of astroviruses to be cultured in CNS-derived cells in vitro has not been reported to date. Both astrovirus VA1/HMO-C (VA1; mamastrovirus 9) and classic human astrovirus 4 (HAstV4; mamastrovirus 1) have been previously detected from cases of human encephalitis. We tested the ability of primary human neurons, primary human astrocytes, and other immortalized human nervous system cell lines (SK-N-SH, U87 MG, and SW-1088) to support infection and replication of these two astrovirus genotypes. Primary astrocytes and SK-N-SH cells supported the full viral life cycle of VA1 with a >100-fold increase in viral RNA levels during a multistep growth curve, detection of viral capsid, and a >100-fold increase in viral titer. Primary astrocytes were permissive with respect to HAstV4 infection and replication but did not yield infectious virus, suggesting abortive infection. Similarly, abortive infection of VA1 was observed in SW-1088 and U87 MG cells. Elevated expression of the chemokine CXCL10 was detected in VA1-infected primary astrocytes and SK-N-SH cells, suggesting that VA1 infection can induce a proinflammatory host response. These findings establish an in vitro cell culture model that is essential for investigation of the basic biology of astroviruses and their neuropathogenic potential.
KW - Astrovirus
KW - Astrovirus VA1
KW - Cell culture
KW - Encephalitis
KW - Virology
UR - http://www.scopus.com/inward/record.url?scp=85069302708&partnerID=8YFLogxK
U2 - 10.1128/mBio.01455-19
DO - 10.1128/mBio.01455-19
M3 - Article
C2 - 31289185
AN - SCOPUS:85069302708
SN - 2161-2129
VL - 10
JO - mBio
JF - mBio
IS - 4
M1 - e01455-19
ER -