Nuclear localization of the human cytomegalovirus tegument protein pp150 (ppUL32)

Hensel, Gabriele; Meyer, Hemmo; Gärtner, Sabine; Brand, Gabriele; Kern, Horst F.

doi:10.1099/0022-1317-76-7-1591

Cited by 54 publications

(65 citation statements)

References 18 publications

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“…As previously described, 51,52,61 we detected the pUL32 protein both at the nucleus and the cytoplasm of the infected cells at late stages of the infection. Nuclear signal was present prior to the AC formation in agreement with previous studies, 51,52 however in our Figure 8. Actin reorganization at the AC in HCMV infected cells.…”

Section: Discussionmentioning

confidence: 84%

“…Moreover, viral protein pp65 has been reported to initially localize at the nucleus of the infected cells and at later times of infection both at the nucleus and the cytoplasm, at the viral AC compartment. 11,50,52 Upon GCV treatment, residual pUL32 and pp65 proteins that are expressed, 62,63 are restricted to their nuclear localization (Fig. 5, g,i and p,r).…”

Section: Discussionmentioning

confidence: 99%

“…Infected cells were stained with the viral nuclear protein pUL44 or with the viral proteins, pp65, pUL97, and pUL32 that were used to define the cytoplasmic area that corresponded to the AC at late stages of the infection, 11,50 although at earlier timepoints they localize at the nucleus. [51][52][53] Specifically, infected fibroblasts with an MOI of 0.5 pfu/cell were fixed and stained for RhoB and each of these viral proteins 2 days post-infection (d.p.i. ), prior to AC formation, as well as 3 d.p.i.…”

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

confidence: 99%

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

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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

confidence: 99%

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

et al. 2015

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“…5B), pp150 foci are not restricted to the cytoplasm but also appear in the nuclei of permissive cells. This is reminiscent to the nucleocytoplasmic distribution of newly synthesized pp150 at late stages of infection (25,26). Considering that nuclear entry of herpesvirus genomes relies on capsid disassembly at nuclear pores (27), the composition of pp150 containing nuclear structures at pre-IE times is yet unclear.…”

Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus tegument protein pp150 acts as a cyclin A2–CDK-dependent sensor of the host cell cycle and differentiation state

Bogdanow

Weisbach

Einem

et al. 2013

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

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Upon cell entry, herpesviruses deliver a multitude of premade virion proteins to their hosts. The interplay between these incoming proteins and cell-specific regulatory factors dictates the outcome of infections at the cellular level. Here, we report a unique type of virion-host cell interaction that is essential for the cell cycle and differentiation state-dependent onset of human cytomegalovirus (HCMV) lytic gene expression. The major tegument 150-kDa phosphoprotein (pp150) of HCMV binds to cyclin A2 via a functional RXL/Cy motif resulting in its cyclin A2-dependent phosphorylation. Alanine substitution of the RXL/Cy motif prevents this interaction and allows the virus to fully escape the cyclin-dependent kinase (CDK)-mediated block of immediate early (IE) gene expression in S/G2 phase that normally restricts the onset of the HCMV replication cycle to G0/G1. Furthermore, the cyclin A2-CDKpp150 axis is also involved in the establishment of HCMV quiescence in NTera2 cells, showing the importance of this molecular switch for differentiation state-dependent regulation of IE gene expression. Consistent with the known nucleocapsid-binding function of pp150, its RXL/Cy-dependent phosphorylation affects gene expression of the parental virion only, suggesting a cis-acting, virus particle-associated mechanism of control. The pp150 homologs of other primate and mammalian CMVs lack an RXL/Cy motif and accordingly even the nearest relative of HCMV, chimpanzee CMV, starts its lytic cycle in a cell cycle-independent manner. Thus, HCMV has evolved a molecular sensor for cyclin A2-CDK activity to restrict its IE gene expression program as a unique level of selflimitation and adaptation to its human host.H erpesviruses are highly adapted to their hosts. This is due to a long coevolutionary process and based on an intricate molecular virus-host interaction network. Interestingly, a significant fraction of herpesviral gene products is already present in the very first phase of infection, after virus entry but before the onset of de novo viral gene expression. These factors originate from the tegument, a characteristic, protein-rich layer within herpesvirus particles, occupying the space between nucleocapsid and virus envelope. Tegument proteins serve a number of important functions. They are involved in the cytoplasmic transport of nucleocapsids, nuclear delivery of viral genomes, immune evasion, and transactivation of immediate early (IE) gene transcription (1). Importantly, they also provide a unique opportunity for the virus to flexibly respond to different cell types and states immediately after entry and set the course for a productive or nonproductive infection at the earliest possible stage.A compelling example for a tegument-derived sensor of the host cell milieu is the 71-kDa phosphoprotein (pp71, also referred to as the UL82 gene product "pUL82") of human cytomegalovirus (HCMV, human herpesvirus 5), a widespread human pathogen. Permissiveness for HCMV depends on the cellular differentiation state (2) and is intimately l...

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“…A controversial point is in which compartment of the cell pp150 initially associates with capsids. Some studies detected nuclear localization of pp150 (64,156), while others detected only cytoplasmic localization (7,157,190). No matter where this interaction takes place, it is likely that the pp150 association with the capsid is one of the steps, if not the earliest step, in tegument assembly.…”

Section: Pp150 (Ul32)mentioning

confidence: 99%

Tegument Proteins of Human Cytomegalovirus

Kalejta

2008

Microbiol Mol Biol Rev

163

149

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SUMMARY Human cytomegalovirus (HCMV) is a common, medically relevant human herpesvirus. The tegument layer of herpesvirus virions lies between the genome-containing capsids and the viral envelope. Proteins within the tegument layer of herpesviruses are released into the cell upon entry when the viral envelope fuses with the cell membrane. These proteins are fully formed and active and control viral entry, gene expression, and immune evasion. Most tegument proteins accumulate to high levels during later stages of infection, when they direct the assembly and egress of progeny virions. Thus, viral tegument proteins play critical roles at the very earliest and very last steps of the HCMV lytic replication cycle. This review summarizes HCMV tegument composition and structure as well as the known and speculated functions of viral tegument proteins. Important directions for future investigation and the challenges that lie ahead are identified and discussed.

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Nuclear localization of the human cytomegalovirus tegument protein pp150 (ppUL32)

Cited by 54 publications

References 18 publications

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

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

Human cytomegalovirus tegument protein pp150 acts as a cyclin A2–CDK-dependent sensor of the host cell cycle and differentiation state

Tegument Proteins of Human Cytomegalovirus

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