Identification of a 709-Amino-Acid Internal Nonessential Region within the Essential Conserved Tegument Protein (p)UL36 of Pseudorabies Virus

ABSTRACT Tegument proteins homologous to the essential herpes simplex virus type 1 UL36 gene product (p)UL36 are conserved throughout the Herpesviridae and constitute the largest herpesvirus-encoded proteins. So far, only limited information is available on their functions, which include complex formation with the (p)UL37 homologs via an N-terminal domain and a deubiquitinating activity in the extreme N terminus. For further analysis we constructed deletion mutants lacking 437, 784, 926, 1,046, 1,217, or 1,557 amino acids (aa) from the C terminus. While none of them supported replication of a pseudorabies virus (PrV) UL36 deletion mutant, a mutant polypeptide with an internal deletion from aa 2087 to 2795, which comprises a proline/alanine-rich region, fully complemented the lethal replication defect. Thus, our data indicate that the extreme C terminus of (p)UL36 fulfills an essential role in PrV replication, while a large internal portion of the C-terminal half of the protein is dispensable for replication in cell culture.

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Herpes Simplex Virus Tegument Protein VP16 Is a Component of Primary Enveloped Virions

Journal of Virology ◽

10.1128/jvi.80.5.2582-2584.2006 ◽

2006 ◽

Vol 80 (5) ◽

pp. 2582-2584 ◽

Cited By ~ 51

Author(s):

Raquel Naldinho-Souto ◽

Helena Browne ◽

Tony Minson

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Pseudorabies Virus ◽

Tegument Protein ◽

Immunogold Electron Microscopy ◽

Virus Particles ◽

Tegument Proteins ◽

Perinuclear Space ◽

Simplex Virus

ABSTRACT Immunogold electron microscopy was used to determine whether the tegument proteins VP13/14, VP22, and VP16 of herpes simplex virus type 1 (HSV1) are components of primary enveloped virions. Whereas VP13/14 and VP22 were not detected in virus particles in the perinuclear space and were present in only mature extracellular virions, VP16 was acquired prior to primary envelopment of the virus at the inner nuclear membrane. This finding highlights potential similarities and differences between HSV1 and the related alphaherpesvirus, pseudorabies virus, in which the homologues of all three of these tegument proteins are not incorporated into the virion until secondary envelopment.

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Physical Interaction between Envelope Glycoproteins E and M of Pseudorabies Virus and the Major Tegument Protein UL49

Journal of Virology ◽

10.1128/jvi.76.16.8208-8217.2002 ◽

2002 ◽

Vol 76 (16) ◽

pp. 8208-8217 ◽

Cited By ~ 94

Author(s):

Walter Fuchs ◽

Barbara G. Klupp ◽

Harald Granzow ◽

Christoph Hengartner ◽

Alexandra Brack ◽

...

Keyword(s):

Gene Product ◽

Pseudorabies Virus ◽

Tegument Protein ◽

Physical Interaction ◽

Virus Maturation ◽

Virus Particles ◽

Tegument Proteins ◽

Infected Cells ◽

Simplex Virus

ABSTRACT Envelope glycoprotein M (gM) and the complex formed by glycoproteins E (gE) and I (gI) are involved in the secondary envelopment of pseudorabies virus (PrV) particles in the cytoplasm of infected cells. In the absence of the gE-gI complex and gM, envelopment is blocked and capsids surrounded by tegument proteins accumulate in the cytoplasm (A. R. Brack, J. Dijkstra, H. Granzow, B. G. Klupp, and T. C. Mettenleiter, J. Virol. 73:5364-5372, 1999). Here we demonstrate by yeast two-hybrid analyses that the cytoplasmic domains of gE and gM specifically interact with the C-terminal part of the UL49 gene product of PrV, which represents a major tegument protein and which is homologous to VP22 of herpes simplex virus type 1. However, deletion of the UL49 gene from PrV had only minor effects on viral replication, and ultrastructural analyses of infected cells confirmed that virus maturation and egress, including secondary envelopment in the cytoplasm, were not detectably affected by the absence of UL49. Moreover, the UL49 gene product was shown to be dispensable for virion localization of gE and gM, and mutants lacking either gE or gM incorporated the UL49 protein efficiently into virus particles. In contrast, a PrV mutant with deletions of gE-gI and gM failed to incorporate the UL49 protein despite apparently unaltered intracytoplasmic UL49 expression. In summary, we describe specific interactions between herpesvirus envelope and tegument proteins which may play a role in secondary envelopment during herpesvirus virion maturation.

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Crystal Structure of the N-Terminal Half of the Traffic Controller UL37 from Herpes Simplex Virus 1

Journal of Virology ◽

10.1128/jvi.01244-17 ◽

2017 ◽

Vol 91 (20) ◽

Cited By ~ 8

Author(s):

Andrea L. Koenigsberg ◽

Ekaterina E. Heldwein

Keyword(s):

Crystal Structure ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Pseudorabies Virus ◽

Surface Region ◽

Tegument Protein ◽

Herpes Simplex Virus 1 ◽

Tegument Proteins ◽

Simplex Virus ◽

Hsv 1

ABSTRACT Inner tegument protein UL37 is conserved among all three subfamilies of herpesviruses. Studies of UL37 homologs from two alphaherpesviruses, herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV), have suggested that UL37 plays an essential albeit poorly defined role in intracellular capsid trafficking. At the same time, HSV and PRV homologs cannot be swapped, which suggests that in addition to a conserved function, UL37 homologs also have divergent virus-specific functions. Accurate dissection of UL37 functions requires detailed maps in the form of atomic-resolution structures. Previously, we reported the crystal structure of the N-terminal half of UL37 (UL37N) from PRV. Here, we report the crystal structure of HSV-1 UL37N. Comparison of the two structures reveals that UL37 homologs differ in their overall shapes, distributions of surface charges, and locations of projecting loops. In contrast, the previously identified R2 surface region is structurally conserved. We propose that within the N-terminal half of UL37, functional conservation is centered within the R2 surface region, whereas divergent structural elements pinpoint regions mediating virus-specific functions and may engage different binding partners. Together, the two structures can now serve as templates for a structure-guided exploration of both conserved and virus-specific functions of UL37. IMPORTANCE The ability to move efficiently within host cell cytoplasm is essential for replication in all viruses. It is especially important in the neuroinvasive alphaherpesviruses, such as human herpes simplex virus 1 (HSV-1), HSV-2, and veterinarian pseudorabies virus (PRV), that infect the peripheral nervous system and have to travel long distances along axons. Capsid movement in these viruses is controlled by capsid-associated tegument proteins, yet their specific roles have not yet been defined. Systematic exploration of the roles of tegument proteins in capsid trafficking requires detailed navigational charts in the form of their three-dimensional structures. Here, we determined the crystal structure of the N-terminal half of a conserved tegument protein, UL37, from HSV-1. This structure, along with our previously reported structure of the UL37 homolog from PRV, provides a much needed 3-dimensional template for the dissection of both conserved and virus-specific functions of UL37 in intracellular capsid trafficking.

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The Capsid and Tegument of the Alphaherpesviruses Are Linked by an Interaction between the UL25 and VP1/2 Proteins

Journal of Virology ◽

10.1128/jvi.01113-07 ◽

2007 ◽

Vol 81 (21) ◽

pp. 11790-11797 ◽

Cited By ~ 105

Author(s):

Kelly Elizabeth Coller ◽

Joy I-Hsuan Lee ◽

Aki Ueda ◽

Gregory Allan Smith

Keyword(s):

Pseudorabies Virus ◽

Fluorescent Protein ◽

Protein Product ◽

Tegument Protein ◽

Viral Propagation ◽

Tegument Proteins ◽

Green Fluorescent ◽

Simplex Virus ◽

Carboxy Terminal ◽

Hsv 1

ABSTRACT How alphaherpesvirus capsids acquire tegument proteins remains a key question in viral assembly. Using pseudorabies virus (PRV), we have previously shown that the 62 carboxy-terminal amino acids of the VP1/2 large tegument protein are essential for viral propagation and when transiently expressed as a fusion to green fluorescent protein relocalize to nuclear capsid assemblons following viral infection. Here, we show that localization of the VP1/2 capsid-binding domain (VP1/2cbd) into assemblons is conserved in herpes simplex virus type 1 (HSV-1) and that this recruitment is specifically on capsids. Using a mutant virus screen, we find that the protein product of the UL25 gene is essential for VP1/2cbd association with capsids. An interaction between UL25 and VP1/2 was corroborated by coimmunoprecipitation from cells transiently expressing either HSV-1 or PRV proteins. Taken together, these findings suggest that the essential function of the VP1/2 carboxy terminus is to anchor the VP1/2 tegument protein to capsids. Furthermore, UL25 encodes a multifunctional capsid protein involved in not only encapsidation, as previously described, but also tegumentation.

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Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways

Microorganisms ◽

10.3390/microorganisms9020292 ◽

2021 ◽

Vol 9 (2) ◽

pp. 292

Author(s):

Miroslava Šudomová ◽

Sherif T. S. Hassan

Keyword(s):

Pseudorabies Virus ◽

Inflammatory Diseases ◽

Bovine Herpesvirus 1 ◽

Dna Viruses ◽

Barr Virus ◽

Clinical Investigations ◽

Epstein Barr ◽

Health Complications ◽

Simplex Virus

Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.

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