TY - JOUR
T1 - Nonenvelopment role for the ESCRTIII complex during human cytomegalovirus infection
AU - Streck, Nicholas T.
AU - Carmichael, Jillian
AU - Buchkovich, Nicholas J.
N1 - Funding Information:
We thank Brianne Roper for assistance in generating reagents. We thank Han Chen and the Penn State Hershey imaging core for the preparation of EM samples. We thank John Wills for helpful discussions, suggestions on preparing the manuscript, and assistance with the HSV-1 studies in his lab. J.C. was supported by John Wills' NIH grant R01AI071286. The work and authors N.J.B and N.T.S. were supported by NIH grant R01AI130156 to N.J.B., by NIH training grant T32CA060395 (N.T.S.), and under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds. The Department specifically disclaims responsibility for any analyses, interpretations, or conclusions. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication
Funding Information:
J.C. was supported by John Wills’ NIH grant R01AI071286. The work and authors N.J.B and N.T.S. were supported by NIH grant R01AI130156 to N.J.B., by NIH training grant T32CA060395 (N.T.S.), and under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds. The Department specifically disclaims responsibility for any analyses, interpretations, or conclusions. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Publisher Copyright:
© 2018 American Society for Microbiology.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Secondary envelopment of human cytomegalovirus (HCMV) occurs through a mechanism that is poorly understood. Many enveloped viruses utilize the endosomal sorting complexes required for transport (ESCRTs) for viral budding and envelopment. Although there are conflicting reports on the role of the ESCRT AAA ATPase protein VPS4 in HCMV infection, VPS4 may act in an envelopment role similar to its function during other viral infections. Because VPS4 is normally recruited by the ESCRT-III complex, we hypothesized that ESCRT-III subunits would also be required for HCMV infection. We investigated the role of ESCRT-III, the core ESCRT scission complex, during the late stages of infection. We show that inducible expression of dominant negative ESCRT-III subunits during infection blocks endogenous ESCRT function but does not inhibit virus production. We also show that HCMV forms enveloped intracellular and extracellular virions in the presence of dominant negative ESCRT-III subunits, suggesting that ESCRT-III is not involved in the envelopment of HCMV. We also found that as with ESCRT-III, inducible expression of a dominant negative form of VPS4A did not inhibit the envelopment of virions or reduce virus titers. Thus, HCMV does not require the ESCRTs for secondary envelopment. However, we found that ESCRT-III subunits are required for efficient virus spread. This suggests a role for ESCRT-III during the spread of HCMV that is independent of viral envelopment.
AB - Secondary envelopment of human cytomegalovirus (HCMV) occurs through a mechanism that is poorly understood. Many enveloped viruses utilize the endosomal sorting complexes required for transport (ESCRTs) for viral budding and envelopment. Although there are conflicting reports on the role of the ESCRT AAA ATPase protein VPS4 in HCMV infection, VPS4 may act in an envelopment role similar to its function during other viral infections. Because VPS4 is normally recruited by the ESCRT-III complex, we hypothesized that ESCRT-III subunits would also be required for HCMV infection. We investigated the role of ESCRT-III, the core ESCRT scission complex, during the late stages of infection. We show that inducible expression of dominant negative ESCRT-III subunits during infection blocks endogenous ESCRT function but does not inhibit virus production. We also show that HCMV forms enveloped intracellular and extracellular virions in the presence of dominant negative ESCRT-III subunits, suggesting that ESCRT-III is not involved in the envelopment of HCMV. We also found that as with ESCRT-III, inducible expression of a dominant negative form of VPS4A did not inhibit the envelopment of virions or reduce virus titers. Thus, HCMV does not require the ESCRTs for secondary envelopment. However, we found that ESCRT-III subunits are required for efficient virus spread. This suggests a role for ESCRT-III during the spread of HCMV that is independent of viral envelopment.
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U2 - 10.1128/JVI.02096-17
DO - 10.1128/JVI.02096-17
M3 - Article
C2 - 29618648
AN - SCOPUS:85047660077
SN - 0022-538X
VL - 92
JO - Journal of virology
JF - Journal of virology
IS - 12
M1 - e02096-17
ER -