TY - JOUR
T1 - Coalescing replication compartments provide the opportunity for recombination between coinfecting herpesviruses
AU - Tomer, Enosh
AU - Cohen, Efrat M.
AU - Drayman, Nir
AU - Afriat, Amichay
AU - Weitzman, Matthew D.
AU - Zaritsky, Assaf
AU - Kobiler, Oren
N1 - Publisher Copyright:
© FASEB
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Homologous recombination (HR) is considered a major driving force of evolution because it generates and expands genetic diversity. Evidence of HR between coinfecting herpesvirus DNA genomes can be found frequently both in vitro and in clinical isolates. Each herpes simplex virus type 1 (HSV-1) replication compartment (RC) derives from a single incoming genome and maintains a specific territory within the nucleus. This raises intriguing questions about where and when coinfecting viral genomes interact. To study the spatiotemporal requirements for intergenomic recombination, we developed an assay with dual-color FISH that enables detection of HR between different pairs of coinfecting HSV-1 genomes. Our results revealed that HR increases intermingling of RCs derived from different genomes. Furthermore, inhibition of RC movement reduces the rate of HR events among coinfecting viruses. Finally, we observed correlation between nuclear size and the number of RCs per nucleus. Our findings suggest that both viral replication and recombination are subject to nuclear spatial constraints. Other DNA viruses and cellular DNA are likely to encounter similar restrictions.—Tomer, E., Cohen, E. M., Drayman, N., Afriat, A., Weitzman, M. D., Zaritsky, A., Kobiler, O. Coalescing replication compartments provide the opportunity for recombination between coinfecting herpesviruses. FASEB J. 33, 9388–9403 (2019). www.fasebj.org.
AB - Homologous recombination (HR) is considered a major driving force of evolution because it generates and expands genetic diversity. Evidence of HR between coinfecting herpesvirus DNA genomes can be found frequently both in vitro and in clinical isolates. Each herpes simplex virus type 1 (HSV-1) replication compartment (RC) derives from a single incoming genome and maintains a specific territory within the nucleus. This raises intriguing questions about where and when coinfecting viral genomes interact. To study the spatiotemporal requirements for intergenomic recombination, we developed an assay with dual-color FISH that enables detection of HR between different pairs of coinfecting HSV-1 genomes. Our results revealed that HR increases intermingling of RCs derived from different genomes. Furthermore, inhibition of RC movement reduces the rate of HR events among coinfecting viruses. Finally, we observed correlation between nuclear size and the number of RCs per nucleus. Our findings suggest that both viral replication and recombination are subject to nuclear spatial constraints. Other DNA viruses and cellular DNA are likely to encounter similar restrictions.—Tomer, E., Cohen, E. M., Drayman, N., Afriat, A., Weitzman, M. D., Zaritsky, A., Kobiler, O. Coalescing replication compartments provide the opportunity for recombination between coinfecting herpesviruses. FASEB J. 33, 9388–9403 (2019). www.fasebj.org.
KW - DNA recombination
KW - herpes simplex virus
KW - nuclear spatial constraints
KW - viral nuclear interactions
UR - http://www.scopus.com/inward/record.url?scp=85070787238&partnerID=8YFLogxK
U2 - 10.1096/fj.201900032R
DO - 10.1096/fj.201900032R
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AN - SCOPUS:85070787238
SN - 0892-6638
VL - 33
SP - 9388
EP - 9403
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -