scholarly journals The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients.

1996 ◽  
Vol 184 (1) ◽  
pp. 283-288 ◽  
Author(s):  
L L Decker ◽  
P Shankar ◽  
G Khan ◽  
R B Freeman ◽  
B J Dezube ◽  
...  

Short DNA sequences have been identified, originally in association with Kaposi's sarcoma (KS) biopsies, that are highly homologous to oncogenic, lymphotropic herpesviruses. Recently a virus, Kaposi sarcoma associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8), bearing these sequences has been identified in a cell line derived from a body cavity-based lymphoma. In this report, we show that the same sequences are present in KS biopsies as DNA molecules of a form and size characteristic of latent herpesviruses-large, covalently closed, circular episomes. The genomes migrate with an apparent size larger than the herpesvirus Epstein-Barr virus (172 kb). This form of the viral genome was found in four of four biopsies and three of five peripheral blood samples from KS patients. Linear forms of the viral genome, characteristic of viral replication, were not detected in the biopsies, but were present in the peripheral blood of three out of five patients. The sequences for KSHV/HHV-8 were also detected in the blood of four of five allograft patients and three of five healthy donors without KS suggesting that the virus is widespread throughout the human population.

PEDIATRICS ◽  
1995 ◽  
Vol 96 (4) ◽  
pp. 783-785
Author(s):  
Tetsuo Hashida ◽  
Emiko Komura ◽  
Maki Yoshida ◽  
Takuji Otsuka ◽  
Shigeyoshi Hibi ◽  
...  

Human herpesvirus-7 (HHV-7), a newly identified lymphotropic member of the herpes family, has recently been isolated from the peripheral blood mononuclear cells (PBMC) of healthy individuals.1 Similar to human herpesvirus-6 (HHV-6), HHV-7 has been found to prevalently infect children at younger ages.2-4 HHV-6 is known to be a causative agent of exanthema subitum,5 and has also been identified in cases of fatal fulminant hepatitis,6 hemophagocytic syndrome,7 encephalitis,8 and intussusception.9 Moreover, HHV-6 infection with severe consequences has been reported in bone marrow and organ transplant patients undergoing immunosuppressive therapy.10-12 Although HHV-7 has recently been isolated from the PBMC of the patients with chronic fatigue syndrome13 and of a child with symptoms mimicking chronic Epstein Barr virus (EBV) infection,14 it is as yet unknown what other diseases are associated with this newly isolated HHV-7 virus infection.


Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 968-976 ◽  
Author(s):  
Maria Caterina Sirianni ◽  
Laura Vincenzi ◽  
Valeria Fiorelli ◽  
Simone Topino ◽  
Enrico Scala ◽  
...  

Abstract Evidence indicates that, at least in the early stage, Kaposi's sarcoma (KS) is a cytokine-mediated disease and that it is consistently associated with a novel herpesvirus termed human herpesvirus-8 (HHV-8). To gain insights into the mechanisms by which cytokines and HHV-8 may cooperate in disease pathogenesis, we examined the phenotype, the Th1 (γ-interferon [γIFN]) and Th2 (interleukin-4 [IL-4]) cytokine profile and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC), tumor-infiltrating lymphocytes (TIL), and spindle cell cultures derived from skin lesions of patients affected by classical KS (C-KS) and acquired immunodeficiency syndrome (AIDS)-associated KS (AIDS-KS). TIL and spindle cell cultures were examined at day 0 or after culture in conditioned media from activated T cells (TCM) that contain the same cytokines increased in KS tissues. No differences were found in the immunophenotype of PBMC from C-KS patients versus controls, except for AIDS-KS patients who showed a T-CD8+ expansion. However, a preferential infiltration of T-CD8+ cells was found in all KS lesions examined, which was maintained after culture of TIL in TCM. γIFN production was found in both PBMC and cultures derived from all KS examined; some IL-4 positive supernatants were found only in three AIDS-KS cases. Uninvolved skin did not show appreciable lymphocyte infiltration or cytokine production. The culture conditions of the lesional skin allowed also the appearance of adherent, spindle-like cells bearing markers of tissue macrophages. Finally, most or all of the PBMC, lesions, and macrophagic cell cultures from the skin lesions were found to be positive for HHV-8 infection by nested polymerase chain reaction (PCR). These findings indicate that patients with KS express a Th1 phenotype with a prevalent γIFN production, likely accounted for by the local T-CD8+ infiltration. By analogy with other viral infections (ie, Epstein-Barr virus), this suggests that in loco recruitment of lymphoid cells and the subsequent γIFN production may be in response to or elicited by HHV-8 that was found in both PBMC and macrophagic cell cultures from the lesions of the same patients.


2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Bettina Heidecker ◽  
Simon H. Williams ◽  
Komal Jain ◽  
Alexandra Oleynik ◽  
Dimitri Patriki ◽  
...  

Background: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood. Methods: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13). Results: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K. Conclusions: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.


Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 297-301 ◽  
Author(s):  
RW Humphrey ◽  
TR O'Brien ◽  
FM Newcomb ◽  
H Nishihara ◽  
KM Wyvill ◽  
...  

Abstract Herpesvirus-like DNA sequences (KSHV/HHV-8) have recently been described in AIDS-associated Kaposi's sarcoma (KS) lesions. Many questions remain regarding the role of this virus in KS and the therapeutic implications of this finding. In the current study, KSHV/HHV-8 DNA was detected in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-infected patients with KS (34/98) more often than in HIV-infected individuals without KS (12/64, P = .03). The detection of KSHV/HHV-8 DNA did not correlate with the CD4 lymphocyte count. Five patients demonstrated KSHV/HHV-8 DNA in their PBMCs during administration of intravenous foscarnet and/or ganciclovir. The continued detection of KSHV/HHV-8 DNA in the PBMCs of patients receiving these anti-herpesvirus drugs has potential implications regarding the virus-cell relationship of KSHV/HHV-8, as well as for the value of these drugs in treating or preventing KS, but additional studies are needed.


1978 ◽  
Vol 148 (5) ◽  
pp. 1429-1434 ◽  
Author(s):  
L Slaughter ◽  
D A Carson ◽  
F C Jensen ◽  
T L Holbrook ◽  
J H Vaughan

Peripheral blood mononuclear cells from 10 patients with rheumatoid arthritis and 9 control subjects were cultured in vitro for 30 days with and without infection by Epstein-Barr virus. All cultures showed polyclonal stimulation of B cells as indicated by rising levels of IgM in the culture supernates, reaching maximal at 18-24 days, and with no quantitative or kinetic difference between the RA and control cells. IgM anti-IgG was also produced in both groups and maximally at 18-24 days, but in greater quantity by the RA lymphocytes. The anti-IgG made by the RA lymphocytes was more easily absorbed by solid phase IgG than was the anti-IgG made by the normal lymphocytes and thus was judged to be of higher affinity. RA lymphocytes uninfected with EBV had higher transformation scores than did the normal controls and developed spontaneously into permanent cell lines in six instances.


2007 ◽  
Vol 81 (10) ◽  
pp. 4919-4927 ◽  
Author(s):  
Frida Hasslung Wikström ◽  
Brian M. Meehan ◽  
Mikael Berg ◽  
Sirje Timmusk ◽  
Josefine Elving ◽  
...  

ABSTRACT DNA sequences containing CpG motifs are recognized as immunomodulators in several species. Phosphodiester oligodeoxyribonucleotides (ODNs) representing sequences from the genome of porcine circovirus type 2 (PCV2) have been identified as potent inducers (ODN PCV2/5) or inhibitors (ODN PCV2/1) of alpha interferon (IFN-α) production by porcine peripheral blood mononuclear cells (poPBMCs) in vitro. In this study, the IFN-α-inducing or -inhibitory activities of specific phosphodiester ODNs were demonstrated to be dependent on their ability to form secondary structures. When a poly(G) sequence was added to a stimulatory self-complementary ODN, high levels of IFN-α were elicited, and the induction was not dependent on pretreatment with the transfecting agent Lipofectin. In addition, the IFN-α-inducing ODN required the presence of an intact CpG dinucleotide, whereas the inhibitory activity of ODN PCV2/1 was not affected by methylation or removal of the central CpG dinucleotide. Of particular significance, the IFN-α inhibition elicited by ODN PCV2/1 was only effective against induction stimulated by DNA control inducers and not RNA control inducers, indicating activity directed to TLR9 signaling. The PCV2 genome as a whole was demonstrated to induce IFN-α in cultures of poPBMCs, and the presence of immune modulatory sequences within the genome of PCV2 may, therefore, have implications with regard to the immune evasion mechanisms utilized by PCV2.


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