scholarly journals Herpes Simplex Virus 1 Glycoprotein B and US3 Collaborate To Inhibit CD1d Antigen Presentation and NKT Cell Function

2011 ◽  
Vol 85 (16) ◽  
pp. 8093-8104 ◽  
Author(s):  
P. Rao ◽  
H. T. Pham ◽  
A. Kulkarni ◽  
Y. Yang ◽  
X. Liu ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antigen Presentation ◽  
Cell Function ◽  
Glycoprotein B ◽  
Nkt Cell ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus 1 Specifically Targets Human CD1d Antigen Presentation To Enhance Its Pathogenicity

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Ping Rao ◽  
Xiangshu Wen ◽  
Jae Ho Lo ◽  
Seil Kim ◽  
Xin Li ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Immune System ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Cell Function ◽  
Nkt Cells ◽  
Nkt Cell ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTHerpes simplex virus 1 (HSV-1) is one of the most prevalent herpesviruses in humans and represents a constant health threat to aged and immunocompromised populations. How HSV-1 interacts with the host immune system to efficiently establish infection and latency is only partially known. CD1d-restricted NKT cells are a critical arm of the host innate immune system and play potent roles in anti-infection and antitumor immune responses. We discovered previously that upon infection, HSV-1 rapidly and efficiently downregulates CD1d expression on the cell surface and suppresses the function of NKT cells. Furthermore, we identified the viral serine/threonine protein kinase US3 as a major viral factor downregulating CD1d during infection. Interestingly, neither HSV-1 nor its US3 protein efficiently inhibits mouse CD1d expression, suggesting that HSV-1 has coevolved with the human immune system to specifically suppress human CD1d (hCD1d) and NKT cell function for its pathogenesis. This is consistent with the fact that wild-type mice are mostly resistant to HSV-1 infection. On the other hand,in vivoinfection of CD1d-humanized mice (hCD1d knock-in mice) showed that HSV-1 can indeed evade hCD1d function and establish infection in these mice. We also report here that US3-deficient viruses cannot efficiently infect hCD1d knock-in mice but infect mice lacking all NKT cells at a higher efficiency. Together, these studies supported HSV-1 evasion of human CD1d and NKT cell function as an important pathogenic factor for the virus. Our results also validated the potent roles of NKT cells in antiherpesvirus immune responses and pointed to the potential of NKT cell ligands as adjuvants for future vaccine development.IMPORTANCEHerpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We reported previously that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule, CD1d, so as to evade the antiviral function of NKT cells. Here we demonstrated that the virus has coevolved with the human CD1d and NKT cell system and that NKT cells indeed play potent roles in anti-HSV immune responses. These studies point to the great potential of exploring NKT cell ligands as adjuvants for HSV vaccines.

scholarly journals Effects of Phosphorylation of Herpes Simplex Virus 1 Envelope Glycoprotein B by Us3 Kinase In Vivo and In Vitro

2009 ◽  
Vol 84 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Takahiko Imai ◽  
Ken Sagou ◽  
Jun Arii ◽  
Yasushi Kawaguchi
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Replication ◽  
Envelope Glycoprotein ◽  
Critical Role ◽  
Glycoprotein B ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT We recently reported that the herpes simplex virus 1 (HSV-1) Us3 protein kinase phosphorylates threonine at position 887 (Thr-887) in the cytoplasmic tail of envelope glycoprotein B (gB) (A. Kato, J. Arii, I. Shiratori, H. Akashi, H. Arase, and Y. Kawaguchi, J. Virol. 83:250-261, 2009; T. Wisner, C. C. Wright, A. Kato, Y. Kawaguchi, F. Mou, J. D. Baines, R. J. Roller and D. C. Johnson, J. Virol. 83:3115-3126, 2009). In the studies reported here, we examined the effect(s) of this phosphorylation on viral replication and pathogenesis in vivo and present data showing that replacement of gB Thr-887 by alanine significantly reduced viral replication in the mouse cornea and development of herpes stroma keratitis and periocular skin disease in mice. The same effects have been reported for mice infected with a recombinant HSV-1 carrying a kinase-inactive mutant of Us3. These observations suggested that Us3 phosphorylation of gB Thr-887 played a critical role in viral replication in vivo and in HSV-1 pathogenesis. In addition, we generated a monoclonal antibody that specifically reacted with phosphorylated gB Thr-887 and used this antibody to show that Us3 phosphorylation of gB Thr-887 regulated subcellular localization of gB, particularly on the cell surface of infected cells.

scholarly journals UL27.5 Is a Novel γ2 Gene Antisense to the Herpes Simplex Virus 1 Gene Encoding Glycoprotein B

1998 ◽  
Vol 72 (7) ◽  
pp. 6056-6064 ◽  
Author(s):  
Yijan E. Chang ◽  
Laura Menotti ◽  
Felix Filatov ◽  
Gabriella Campadelli-Fiume ◽  
Bernard Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Chimeric Protein ◽  
Open Reading Frame ◽  
Glycoprotein B ◽  
Virus Protein ◽  
Gene Encoding ◽  
Herpes Simplex Virus 1 ◽  
Reading Frame ◽  
Simplex Virus

ABSTRACT An antibody made against the herpes simplex virus 1 US5 gene predicted to encode glycoprotein J was found to react strongly with two proteins, one with an apparent M r of 23,000 and mapping in the S component and one with a herpes simplex virus protein with an apparent M r of 43,000. The antibody also reacted with herpes simplex virus type 2 proteins forming several bands with apparent M rs ranging from 43,000 to 50,000. Mapping studies based on intertypic recombinants, analyses of deletion mutants, and ultimately, reaction of the antibody with a chimeric protein expressed by in-frame fusion of the glutathione S-transferase gene to an open reading frame antisense to the gene encoding glycoprotein B led to the definitive identification of the new open reading frame, designated UL27.5. Sequence analyses indicate the conservation of a short amino acid sequence common to US5 and UL27.5. The coding sequence of the herpes simplex virus UL27.5 open reading frame is strongly homologous to the sequence encoding the carboxyl terminus of the herpes simplex virus 2 UL27.5 sequence. However, both open reading frames could encode proteins predicted to be significantly larger than the mature UL27.5 proteins accumulating in the infected cells, indicating that these are either processed posttranslationally or synthesized from alternate, nonmethionine-initiating codons. The UL27.5 gene expression is blocked by phosphonoacetate, indicating that it is a γ2 gene. The product accumulated predominantly in the cytoplasm. UL27.5 is the third open reading frame found to map totally antisense to another gene and suggests that additional genes mapping antisense to known genes may exist.

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