Human cytomegalovirus final envelopment on membranes containing both<i>trans</i>-Golgi network and endosomal markers

Cepeda, Victoria; Esteban, Mariano; Fraile-Ramos, Alberto

doi:10.1111/j.1462-5822.2009.01405.x

Cited by 84 publications

(127 citation statements)

References 47 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…The AC is thought to be where virions acquire tegument proteins and envelopes. Early endosome antigen-1 (EEA1) is a cellular protein present in early endosomes (35) that participates in endosomal membrane fusion (36) and is localized to the AC within infected cells (37,38). Our findings confirm these characteristics, showing that EEA1 was colocalized with two markers of the AC, a Golgi component targeted by HPA lectin and the late viral protein pUL99 (Fig.…”

supporting

confidence: 78%

Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles

Sharon-Friling

Shenk

2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The human cytomegalovirus immediate-early protein pUL37x1 induces the release of Ca 2+ stores from the endoplasmic reticulum into the cytosol. This release causes reorganization of the cellular actin cytoskeleton with concomitant cell rounding. Here we demonstrate that pUL37x1 activates Ca 2+ -dependent protein kinase Cα (PKCα). Both PKCα and Rho-associated protein kinases are required for actin reorganization and cell rounding; however, only PKCα is required for the efficient production of virus progeny, arguing that HCMV depends on the kinase for a second function. PKCα activation is also needed for the production of large (1-5 μm) cytoplasmic vesicles late after infection. The production of these vesicles is blocked by inhibition of fatty acid or phosphatidylinositol-3-phosphate biosynthesis, and the failure to produce vesicles is correlated with substantially reduced production of enveloped virus capsids. These results connect earlier work identifying a requirement for lipid synthesis with specific morphological changes, and support the argument that the PKCα-induced large vesicles are either required for the efficient production of mature virus particles or serve as a marker for the process.capsid envelopment | virion assembly | virus-induced membranes

show abstract

supporting

confidence: 78%

Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles

Sharon-Friling

Shenk

2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…1G upper panel), an observation in line with the fact that other TGN markers, such as TGN-46 and p230, also localize at the AC. 6,7,11,50,54 Live cell imaging using an autofluorescent RhoB construct, mRFP-RhoB, and the recombinant UL32-EGFP-HCMV-TB40 virus, not only confirmed the observations from the experiments in fixed cells but additionally shed light into the dynamics of RhoB spatial localization in association with the pUL32 tegument protein at the late stages of HCMV infection. Apart from its marked upregulation, RhoB is also relocated during viral infection, changing from an initial cytoplasmic, relatively scattered distribution to a striking recruitment to sites where new virions are assembled, along with structural HCMV proteins, such as pUL32 ( Fig.…”

Section: Discussionsupporting

confidence: 55%

“…1G lower panel). The same pattern of subcellular association has been observed among several TGN markers, Rab5 and HCMV AC proteins 6,7,11,54 corroborating the specificity of RhoB localization in the assembly site of the virus. …”

Section: Rhob Is Upregulated Upon Hcmv Infection and Localizes At Thesupporting

confidence: 57%

“…This is of interest, as it has been reported that the cellular proteins, CD63, TGN46 and CD-M6PR, that also localize at the AC are downregulated in infected cells and are incorporated in new virions. 7 During the formation of the AC, extensive cytoplasmic remodeling occurs, resulting in dramatic reorientation of the secretory machinery, including the early endosomes. 6,7,10,14 Although RhoB has been reported to localize to early endosomes, 20 it is not fully spatially associated with the early endosome protein Rab5 65,66 in HCMV-infected cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The endosomal sorting complex required for transport (ESCRT) machinery and multivesicular bodies (MVB) play a role in virion maturation. [6][7][8][9][10][11][12][13][14] RhoB belongs to the Rho GTPase family of proteins that comprises 6 subfamilies. 15 The RhoA subfamily consists of RhoA, RhoB and RhoC, which exhibit approximately 85% amino acid sequence identity.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

et al. 2015

View full text Add to dashboard Cite

Human Cytomegalovirus (HCMV), an ubiquitous b-herpesvirus, is a significant pathogen that causes medically severe diseases in immunocompromised individuals and in congenitally infected neonates. RhoB belongs to the family of Rho GTPases, which regulates diverse cellular processes. Rho proteins are implicated in the entry and egress from the host cell of mainly a-and g-herpesviruses, whereas b-herpesviruses are the least studied in this regard. Here, we studied the role of RhoB GTPase during HCMV lytic infection. Microscopy analysis, both in fixed and live infected cells showed that RhoB was translocated to the assembly complex/compartment (AC) of HCMV, a cytoplasmic zone in infected cells where many viral structural proteins are known to accumulate and assembly of new virions takes place. Furthermore, RhoB was localized at the AC even when the expression of the late HCMV AC proteins was inhibited. At the very late stages of infection, cellular projections were formed containing RhoB and HCMV virions, potentially contributing to the successful viral spread. Interestingly, the knockdown of RhoB in HCMV-infected cells resulted in a significant reduction of the virus titer and could also affect the accumulation of AC viral proteins at this subcellular compartment. RhoB knockdown also affected actin fibers' structure. Actin reorganization was observed at late stages of infection originating from the viral AC and surrounding the cellular projections, implying a potential interplay between RhoB and actin during HCMV assembly and egress. In conclusion, our results demonstrate for the first time that RhoB is a constituent of the viral AC and is required for HCMV productive infection.

show abstract

Betaherpesvirus Virion Assembly and Egress

Anderson

Pellett

2018

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Virions are the vehicle for cell-to-cell and host-to-host transmission of viruses. Virions need to be assembled reliably and efficiently, be released from infected cells, survive in the extracellular environment during transmission, recognize and then trigger entry of appropriate target cells, and disassemble in an orderly manner during initiation of a new infection. The betaherpesvirus subfamily includes four human herpesviruses (human cytomegalovirus and human herpesviruses 6A, 6B, and 7), as well as viruses that are the basis of important animal models of infection and immunity. Similar to other herpesviruses, betaherpesvirus virions consist of four main parts (in order from the inside): the genome, capsid, tegument, and envelope. Betaherpesvirus genomes are dsDNA and range in length from ~145 to 240 kb. Virion capsids (or nucleocapsids) are geometrically well-defined vessels that contain one copy of the dsDNA viral genome. The tegument is a collection of several thousand protein and RNA molecules packed into the space between the envelope and the capsid for delivery and immediate activity upon cellular entry at the initiation of an infection. Betaherpesvirus envelopes consist of lipid bilayers studded with virus-encoded glycoproteins; they protect the virion during transmission and mediate virion entry during initiation of new infections. Here, we summarize the mechanisms of betaherpesvirus virion assembly, including how infection modifies, reprograms, hijacks, and otherwise manipulates cellular processes and pathways to produce virion components, assemble the parts into infectious virions, and then transport the nascent virions to the extracellular environment for transmission.

show abstract

Human cytomegalovirus final envelopment on membranes containing bothtrans-Golgi network and endosomal markers

Cited by 84 publications

References 47 publications

Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles

Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

Betaherpesvirus Virion Assembly and Egress

Contact Info

Product

Resources

About