The small 11kDa nonstructural protein of human parvovirus B19 plays a key role in inducing apoptosis during B19 virus infection of primary erythroid progenitor cells

AY Chen, EY Zhang, W Guan, F Cheng… - Blood, The Journal …, 2010 - ashpublications.org
AY Chen, EY Zhang, W Guan, F Cheng, S Kleiboeker, TM Yankee, J Qiu
Blood, The Journal of the American Society of Hematology, 2010ashpublications.org
Abstract Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and
drastically destroys erythroid progenitor cells, thus leading to most of the disease outcomes
associated with B19V infection. In this study, we systematically examined the 3 B19V
nonstructural proteins, 7.5 kDa, 11kDa, and NS1, for their function in inducing apoptosis in
transfection of primary ex vivo–expanded erythroid progenitor cells, in comparison with
apoptosis induced during B19V infection. Our results show that 11kDa is a more significant …
Abstract
Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and drastically destroys erythroid progenitor cells, thus leading to most of the disease outcomes associated with B19V infection. In this study, we systematically examined the 3 B19V nonstructural proteins, 7.5kDa, 11kDa, and NS1, for their function in inducing apoptosis in transfection of primary ex vivo–expanded erythroid progenitor cells, in comparison with apoptosis induced during B19V infection. Our results show that 11kDa is a more significant inducer of apoptosis than NS1, whereas 7.5kDa does not induce apoptosis. Furthermore, we determined that caspase-10, an initiator caspase in death receptor signaling, is the most active caspase in apoptotic erythroid progenitors induced by 11kDa and NS1 as well as during B19V infection. More importantly, cytoplasm-localized 11kDa is expressed at least 100 times more than nucleus-localized NS1 at the protein level in primary erythroid progenitor cells infected with B19V; and inhibition of 11kDa expression using antisense oligos targeting specifically to the 11kDa-encoding mRNAs reduces apoptosis significantly during B19V infection of erythroid progenitor cells. Taken together, these results demonstrate that the 11kDa protein contributes to erythroid progenitor cell death during B19V infection.
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