Expression of human herpesvirus 6 (HHV-6) genes in virus-infected cells

2005 ◽  
Author(s):  
Yuen-kei, Vivien Fok
Keyword(s):  
Human Herpesvirus ◽  
Human Herpesvirus 6 ◽  
Infected Cells ◽  
Herpesvirus 6

scholarly journals Immunosuppressive effect of human herpesvirus 6 on T-cell functions: suppression of interleukin-2 synthesis and cell proliferation [published erratum appears in Blood 1995 Jul 1;86(1):418]

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1263-1271 ◽  
Author(s):  
L Flamand ◽  
J Gosselin ◽  
I Stefanescu ◽  
D Ablashi ◽  
J Menezes
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Cellular Proliferation ◽  
Interleukin 2 ◽  
Human Herpesvirus ◽  
Human Herpesvirus 6 ◽  
Infected Cells ◽  
Herpesvirus 6

Human herpesvirus-6 (HHV-6), the etiologic agent of roseola, is ubiquitous, establishes latency in the host, and can infect a variety of immunocompetent cells, with CD4+ T lymphocytes being the targets in which it replicates most efficiently. The present study was undertaken to learn more about specific immunobiologic effects of HHV-6 infection on T-lymphocyte functions. Our data demonstrate that infection of peripheral blood mononuclear cells (PBMC) by HHV-6 results in suppression of T-lymphocyte functions, as evidenced by reduced interleukin-2 (IL-2) synthesis and cellular proliferation. In fact, HHV- 6-infected PBMC secreted 50% less IL-2 than mock-infected cells after mitogenic stimulation with OKT3 antibody or phytohemmaglutinin (PHA). The inhibition of IL-2 by HHV-6 was also observed in enriched T-cell cultures, suggesting a direct effect of this virus on this cell type. Messenger RNA (mRNA) analysis by reverse-transcriptase polymerase chain reaction (PCR) indicated that HHV-6 diminishes IL-2 mRNA levels in mitogen-stimulated peripheral blood T cells. These results were also confirmed by Northern blot using the leukemic T-cell line Jurkat. This inhibitory effect of HHV-6 did not require infectious virus, as the use of UV-irradiated HHV-6 produced similar results. Moreover, HHV-6- infected PBMC showed up to an 85% reduction in their mitogen-driven proliferative response, as compared with sham-infected cells. Proliferation of both CD4+ and CD8+ T cells was affected by HHV-6. Taken together, our data show that infection of T cells by HHV-6 results in immune suppression characterized by a downregulation of IL-2 mRNA and protein synthesis accompanied by diminished cellular proliferation.

scholarly journals In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6).

1988 ◽  
Vol 167 (5) ◽  
pp. 1659-1670 ◽  
Author(s):  
P Lusso ◽  
P D Markham ◽  
E Tschachler ◽  
F di Marzo Veronese ◽  
S Z Salahuddin ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Population ◽  
Mononuclear Cells ◽  
Human Herpesvirus ◽  
Human Herpesvirus 6 ◽  
Infected Cells ◽  
Cellular Tropism ◽  
Herpesvirus 6

We investigated the cellular tropism of human B-lymphotropic virus (HBLV) (also designated Human Herpesvirus-6) in vitro by infecting fresh MN cells from normal human adult peripheral blood, umbilical cord blood, bone marrow, tonsil, and thymus. Cultures from all the sources examined contained infectable cells, as shown by the appearance of characteristic enlarged, round-shaped, short-lived cells expressing HBLV-specific markers. Detailed immunological analysis demonstrated that the vast majority of these cells expressed T cell-associated antigens (i.e., CD7, CD5, CD2, CD4, and to a lesser extent, CD8). The CD3 antigen and the TCR-alpha/beta heterodimer were not detectable on the surface membrane, but were identified within the cytoplasm of HBLV-infected cells, by both immunofluorescence and radioimmunoprecipitation assay. A proportion of the HBLV-infected cell population also expressed the CD15 and class II MHC DR antigens. By means of immunoselection procedures it was possible to show that a consistent proportion of HBLV-infectable cells were contained within the CD3-depleted immature T cell population, while the depletion of CD2+ cells completely abrogated the infectability of the cultures. Northern blot analysis confirmed the T cell origin of HBLV-infected cells, demonstrating the expression of full size TCR-alpha and -beta chain mRNA. In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL-2 for greater than 30 d. These results indicate that HBLV is selectively T cell tropic in the course of the in vitro infection of normal mononuclear cells and may therefore be directly involved in the pathogenesis of T cell related hematological disorders. In particular, in light of the cytopathic effect exerted in vitro on CD4+ T lymphocytes, a possible role of HBLV in immune deficiency conditions should be considered.

scholarly journals Intracellular Processing of Human Herpesvirus 6 Glycoproteins Q1 and Q2 into Tetrameric Complexes Expressed on the Viral Envelope

2004 ◽  
Vol 78 (15) ◽  
pp. 7969-7983 ◽  
Author(s):  
Pilailuk Akkapaiboon ◽  
Yasuko Mori ◽  
Tomohiko Sadaoka ◽  
Sayoko Yonemoto ◽  
Koichi Yamanishi
Keyword(s):  
Monoclonal Antibody ◽  
Endoplasmic Reticulum ◽  
Human Herpesvirus ◽  
Viral Envelope ◽  
Human Herpesvirus 6 ◽  
Pulse Period ◽  
Viral Particles ◽  
Infected Cells ◽  
Herpesvirus 6 ◽  
Additional Product

ABSTRACT Human herpesvirus 6 (HHV-6) glycoproteins H and L (gH and gL, respectively) and the 80-kDa form of glycoprotein Q (gQ-80K) form a heterotrimeric complex that is found on the viral envelope and that is a viral ligand for human CD46. Besides gQ-80K, the gQ gene encodes an additional product whose mature molecular mass is 37 kDa (gQ-37K) and which is derived from a different transcript. Therefore, we designated gQ-80K as gQ1 and gQ-37K as gQ2. We show here that gQ2 also interacts with the gH-gL-gQ1 complex in HHV-6-infected cells and in virions. To examine how these components interact in HHV-6-infected cells, we performed pulse-chase studies. The results demonstrated that gQ2-34K, which is endo-β-N-acetylglucosaminidase H sensitive and which is the precursor form of gQ2-37K, associates with gQ1-74K, which is the precursor form of gQ1-80K, within 30 min of the pulse period. After a 1-h chase, these precursor forms had associated with the gH-gL dimer. Interestingly, an anti-gH monoclonal antibody coimmunoprecipitated mainly gQ1-80K and gQ2-37K, with little gQ1-74K or gQ2-34K. These results indicate that although gQ2-34K and gQ1-74K interact in the endoplasmic reticulum, the gH-gL-gQ1-80K-gQ2-37K heterotetrameric complex arises in the post-endoplasmic reticulum compartment. The mature complex is subsequently incorporated into viral particles.

scholarly journals The Human Herpesvirus 6 U100 Gene Product Is the Third Component of the gH-gL Glycoprotein Complex on the Viral Envelope

2003 ◽  
Vol 77 (4) ◽  
pp. 2452-2458 ◽  
Author(s):  
Yasuko Mori ◽  
Pilailuk Akkapaiboon ◽  
Xuwei Yang ◽  
Koichi Yamanishi
Keyword(s):  
Viral Entry ◽  
Human Herpesvirus ◽  
Viral Envelope ◽  
Gene Products ◽  
Human Herpesvirus 6 ◽  
Glycoprotein Complex ◽  
The Third ◽  
Glycoprotein H ◽  
Infected Cells ◽  
Herpesvirus 6

ABSTRACT The human herpesvirus 6 (HHV-6) variant A U100 gene encodes the third component of the glycoprotein H (gH)-glycoprotein L (gL)-containing complex. Glycosidase digestion analysis showed that the U100 gene products are glycoproteins consisting of an 80-kDa protein with complex N-linked oligosaccharides and a 74-kDa protein with immature, high-mannose N-linked oligosaccharides. Based on these characteristics, we designated the U100 gene products glycoprotein Q (gQ). Only the 80-kDa form of gQ was coimmunoprecipitated with an anti-gH antibody, suggesting that the 80-kDa protein associates with the gH-gL complex in HHV-6-infected cells. Furthermore, the complex was detected in purified virions, suggesting that it may play an important role in viral entry.

The replication of viral and cellular DNA in human herpesvirus 6-infected cells

Virology ◽  
1990 ◽  
Vol 175 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Dario Di Luca ◽  
George Katsafanas ◽  
Eric C. Schirmer ◽  
N. Balachandran ◽  
Niza Frenkel
Keyword(s):  
Human Herpesvirus ◽  
Human Herpesvirus 6 ◽  
Infected Cells ◽  
Herpesvirus 6 ◽  
Cellular Dna

scholarly journals Identification of Human Herpesvirus 6 Latency-Associated Transcripts

2002 ◽  
Vol 76 (8) ◽  
pp. 4145-4151 ◽  
Author(s):  
Kazuhiro Kondo ◽  
Kazuya Shimada ◽  
Junji Sashihara ◽  
Keiko Tanaka-Taya ◽  
Koichi Yamanishi
Keyword(s):  
Human Herpesvirus ◽  
Immediate Early ◽  
Human Herpesvirus 6 ◽  
Coding Region ◽  
Transcription Start ◽  
Protein Coding ◽  
Transcription Start Sites ◽  
Latently Infected ◽  
Infected Cells ◽  
Herpesvirus 6

ABSTRACT Four kinds of latency-associated transcripts of human herpesvirus 6 were identified which were detected only in latently infected cells. Although they were oriented in the same direction as the immediate-early 1 and 2 (IE1/IE2) genes and shared their protein-coding region with IE1/IE2, their transcription start sites and exon(s) were latency associated.

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