Intracellular Trafficking and Maturation of Herpes Simplex Virus Type 1 gB and Virus Egress Require Functional Biogenesis of Multivesicular Bodies

Calistri, Arianna; Sette, Paola; Salata, Cristiano; Cancellotti, Enrico; Forghieri, Cristina; Comin, Alessandra; Göttlinger, Heinrich G.; Campadelli-Fiume, Gabriella; Palù, Giorgio; Parolin, Cristina

doi:10.1128/jvi.01364-07

Cited by 109 publications

(114 citation statements)

References 85 publications

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“…In addition to HCMV, MVBs and ESCRT machinery have been shown to play a role in the assembly and egress of numerous viruses, including Marburg virus (79), retroviruses (80)(81)(82)(83), hepatitis B virus (84), herpes simplex virus 1 (HSV-1) (85-88), Epstein-Barr virus (89), and human herpesvirus 6 (77,90). Blocking MVB formation by targeting either Vps4 or Vps24 of the ESCRT-III complex during HSV infection results in a dramatic reduction in the yield of cell-associated and cell-free virus, depending on the cell type infected (85,86,88). In HIV infection, the virus buds directly into MVBs in monocytic cells, whereas MVBs are recruited to the plasma membrane to become a site of budding in lymphocytic cells (80).…”

Section: Discussionmentioning

confidence: 99%

An Endothelial Cell-Specific Requirement for the UL133-UL138 Locus of Human Cytomegalovirus for Efficient Virus Maturation

Bughio

Elliott

Goodrum

2013

J Virol

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Human cytomegalovirus (HCMV) infects a variety of cell types in humans, resulting in a varied pathogenesis in the immunocompromised host. Endothelial cells (ECs) are considered an important target of HCMV infection that may contribute to viral pathogenesis. Although the viral determinants important for entry into ECs are well defined, the molecular determinants regulating postentry tropism in ECs are not known. We previously identified the UL133-UL138 locus encoded within the clinical strain-specific ULb= region of the HCMV genome as important for the latent infection in CD34؉ hematopoietic progenitor cells (HPCs). Interestingly, this locus, while dispensable for replication in fibroblasts, was required for efficient replication in ECs infected with the TB40E or fusion-inducing factor X (FIX) HCMV strains. ECs infected with a virus lacking the entire locus (UL133-UL138 NULL virus) complete the immediate-early and early phases of infection but are defective for infectious progeny virus production. ECs infected with UL133-UL138 NULL virus exhibited striking differences in the organization of intracellular membranes and in the assembly of mature virions relative to ECs infected with wild-type (WT) virus. In UL133-UL138 NULL virus-infected ECs, Golgi stacks were disrupted, and the viral assembly compartment characteristic of HCMV infection failed to form. Further, progeny virions in UL133-UL138 NULL virus-infected ECs inefficiently acquired the virion tegument and secondary envelope. These defects were specific to infection in ECs and not observed in fibroblasts infected with UL133-UL138 NULL virus, suggesting an EC-specific requirement for the UL133-UL138 locus for late stages of replication. To our knowledge, the UL133-UL138 locus represents the first cell-type-dependent, postentry tropism determinant required for viral maturation.

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Section: Discussionmentioning

confidence: 99%

An Endothelial Cell-Specific Requirement for the UL133-UL138 Locus of Human Cytomegalovirus for Efficient Virus Maturation

Bughio

Elliott

Goodrum

2013

J Virol

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“…Other HSV-1 genes associated with syn phenotypes are gB, UL20 and gK. gB is involved in entry and egress, both processes that involve fusion (Calistri et al, 2007;Wright et al, 2009;reviewed by Spear & Longnecker, 2003). UL20 and gK are involved in secondary envelopment of virions (Baines et al, 1991;Foster & Kousoulas, 1999;Fuchs et al, 1997;Hutchinson & Johnson, 1995;Jayachandra et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Differential importance of highly conserved residues in UL24 for herpes simplex virus 1 replication in vivo and reactivation

Leiva‐Torres

Rochette

Pearson

2010

Journal of General Virology

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The UL24 gene of herpes simplex virus 1 (HSV-1) is widely conserved among all subfamilies of the Herpesviridae. It is one of only four HSV-1 genes for which mutations have been mapped that confer a syncytial plaque phenotype. In a mouse model of infection, UL24-deficient viruses exhibit reduced titres, particularly in neurons, and an apparent defect in reactivation from latency. There are several highly conserved residues in UL24; however, their importance in the role of UL24 in vivo is unknown. In this study, we compared virus strains with substitution mutations corresponding to the PD-(D/E)XK endonuclease motif of UL24 (vUL24-E99A/K101A) or a substitution of another highly conserved residue (vUL24-G121A). Both mutant viruses cause the formation of syncytial plaques at 39 6C; however, we found that the viruses differed dramatically when tested in a mouse model of infection. vUL24-E99A/K101A exhibited titres in the eye that were 10-fold lower than those of the wild-type virus KOS, and titres in trigeminal ganglia (TG) that were more than 2 log 10 lower. Clinical signs were barely detectable with vUL24-E99A/K101A. Furthermore, the percentage of TG from which virus reactivated was also significantly lower for this mutant than for KOS. In contrast, vUL24-G121A behaved similarly to the wild-type virus in mice. These results are consistent with the endonuclease motif being important for the role of UL24 in vivo and also imply that the UL24 temperature-dependent syncytial plaque phenotype can be separated genetically from several in vivo phenotypes.

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“…Moreover, the site of intracellular gB varies, indicating that gB is dependent on the exosomal pathway. The intracellular trafficking of gB and the envelopment/egress of HSV-1 rely on MVB biogenesis (Calistri et al, 2007). This further suggests that the sorting of gB into MVB membranes is obligatory for the formation of mature HSV-1 and that modified MVB membranes provide a platform for the recruitment of MVB components to allow virus envelopment and egress.…”

Section: Exosomes In Alpha Herpesvirus Infectionmentioning

confidence: 99%

Extracellular vesicles: novel vehicles in herpesvirus infection

et al. 2017

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Herpesviruses are remarkable pathogens that have evolved multiple mechanisms to evade host immunity, ensuring their proliferation and egress. Among these mechanisms, herpesviruses utilize elaborate extracellular vesicles, including exosomes, for the intricate interplay between infected host and recipient cells. Herpesviruses incorporate genome expression products and direct cellular products into exosomal cargoes. These components alter the content and function of exosomes released from donor cells, thus affecting the downstream signalings of recipient cells. In this way, herpesviruses hijack exosomal pathways to ensure their survival and persistence, and exosomes are emerging as critical mediators for virus infection-associated intercellular communication and microenvironment alteration. In this review, the function and effects of exosomes in herpesvirus infection will be discussed, so that we will have a better understanding about the pathogenesis of herpesviruses.

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Intracellular Trafficking and Maturation of Herpes Simplex Virus Type 1 gB and Virus Egress Require Functional Biogenesis of Multivesicular Bodies

Cited by 109 publications

References 85 publications

An Endothelial Cell-Specific Requirement for the UL133-UL138 Locus of Human Cytomegalovirus for Efficient Virus Maturation

An Endothelial Cell-Specific Requirement for the UL133-UL138 Locus of Human Cytomegalovirus for Efficient Virus Maturation

Differential importance of highly conserved residues in UL24 for herpes simplex virus 1 replication in vivo and reactivation

Extracellular vesicles: novel vehicles in herpesvirus infection

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