Genital Herpes

Herpes simplex virus type 2–specific CD8 cytotoxic T lymphocyte cross-reactivity against prevalent HLA class I alleles

Background. In the United States, one out of five of the total adolescent and adult population are infected with herpes simplex virus. Most productive infections are called cytocidal (cytolytic) because they kill the host cell. In this study we investigated the infection of mature DC with herpes simplex virus type 1 (HSV-1) and the way in which infection alters the phenotype and function of mature DC. We produced a PEL cell line derivative containing both latent KSHV genomes and an inducible ORF50ΔSTAD. Within the host cell the genetic material of a DNA virus is replicated and transcribed into messenger RNA by host cell enzymes, and proteins coded for by viral genes are synthesized by host cell ribosomes. Subsequently we focused on differential histone modification as another epigenetic mechanism that could regulate latent transcription.

The plus or “barbed” end of a growing actin filament rapidly elongates while the minus or “pointed” end remains relatively static. Viral lesions of molluscum contagiosum and human papillomavirus have been observed in benign skin proliferations. Despite suppressive or episodic therapy with antivirals, reactivation, with peripheral lytic replication, still occurs in many patients, either as a consequence of antiviral drug resistance or after the cessation of routine antiviral prophylaxis.7 HSV provokes a significant CD8 and CD4 response, despite multiple virally encoded immune evasion genes. Other than the cowpox mentioned above, there are a few vaccines that are delivered as live-attenuated viruses, for example OPV (Oral Polio Vaccine) is a live-attenuated virus, but it also occasionally leads to a vaccine associated disease. Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004) and higher TGF-β expression (p = 0.002) were demonstrated in viral cases. We report 2 examples of HLA A2–restricted CD8 CTL cross-reactivity between HSV-2 and prevalent HLA class I molecules in the HLA B44/45 family, and we outline clinical situations in which these molecular interactions may be medically significant. Patients gave informed consent in accordance with the Helsinki protocol.

Protocols were approved by the University of Washington Institutional Review Board. HSV serostatus was tested by type-specific serology.9 Biopsies of recurrent, HSV-2 culture–positive10 lesions were performed as described.11 PBMCs were isolated by Ficoll-Hypaque density gradient centrifugation and cryopreserved. CD8+ CTL clones 1874.1991.22 and 5101.1999.23 were cultured from biopsies of HSV-2 culture–positive genital lesions of patients 1874 and 5101 (Table 1), without secondary in vitro stimulation with antigen.12 The clones were CD3+ and T-cell receptor αβ (TCR-αβ)+ by flow cytometry, each lysed autologous HSV-2 infected cells, and were proven to be HLA A*0201–restricted by release of IFN-γ after coculture with Cos-7 cells cotransfected with A*0201 cDNA and infected with HSV-2.12 For each clone, lysis of certain HLA class I–mismatched, uninfected EBV-LCLs was observed during initial workup (not shown). Higher KSHV antibody titers are themselves associated with the development of KS [18, 19], although very high titers might be protective against KS lesions [20]. Women who know that they have had genital herpes or think they might have it during pregnancy should tell their physician so preventive measures can be taken. The long-term cellular changes may result in severe disease, immune suppression or may trigger immune responses to damaged, or undamaged cells or tissues. In the murine system, for instance, DC are the most effective antigen-presenting cells in stimulating recall cytotoxic T-lymphocyte (CTL) responses to Sendai virus, Moloney murine leukemia virus (17), HSV (14), and influenza virus (22).

Several of these viral proteins can transform cells (12, 13). In the lentiviruses, it was formerly mistakenly believed that virus was inactive during this period. No need to wait Until You Have a full blown ob – the sooner you can start the meds the faster they Work. Initiation of phagocytosis involves receptor-mediated rearrangement of cortical actin localized near the position of the stimulating particle. A C1R transfectant was not available, but lysis of 2 separate B*4404 cell lines was noted. To begin to examine alloreactivity among HSV-2 VP13/14-specific CD8 CTLs in the population, we generated 2 CD8 CTL clones from the PBMCs of another HSV-2–infected, A*0201-bearing patient (9383, Table 1) by using peptide 289-298. Clones were screened for lysis of A*0201-bearing, HSV-2 infected cells.

Each HSV-2–reactive clone recognized VP13/14 289-298 in the context of A*0201 (Table2). Clone 33 also recognized EBV-LCL bearing the B*4402 allele. Clones 31 and 32 did not lyse wild-type LCLs expressing known B44 alleles, indicating that the response to VP13/14 289-298 for patient 9383 is heterogeneous and contains both cross-reactive and non–cross-reactive clonotypes. However, clone 31 lysed a cell line bearing the related B*4501 allele. Unfortunately, these clones could not be recovered from cryopreservation, so reactivity with defined C1R transfectants or extended panels of wild-type EBV-LCLs could not be performed. It is also possible, therefore, that T-cell clones 9383.33 and 9383.31 recognize other class I or class II determinants expressed by the target cells listed in Table 2. The heterozygous GC genotype of the interleukin (IL)-6 promoter was found to be strongly associated with susceptibility to KS in HIV-infected men.

There may be painful urination, and swollen and tender lymph glands in the groin. Cultured cells that are infected by most viruses undergo morphologic changes, which can be observed easily in unfixed, unstained cells by a light microscope. The cells were inoculated either with infectious HSV-1 (strain ang) (21) at a multiplicity of infection (MOI) of 0.01, 0.1, or 1 or with UV-inactivated HSV-1 for 1 h at 37°C. RTA acts together with cellular proteins, such as Oct1 and HMGB1 (15), SWI/SNF and TRAP/Mediator (14), and recombination signal binding protein Jκ RBPj-κ (or CBF-1 or CSL) (23, 48) to transactivate other genes. For this reason there are no chemotherapeutic agents for most viral diseases. Results are representative of 3 experiments. Nuclear genomes are used as templates for viral transcription, which occurs in three temporal stages [16,17].

In each case, the allogeneic target structures probably contain a member of the HLA B44 family. HLA B44 alleles, although distinct, have related predicted amino acid sequences and peptide-binding motifs.24 Although TCR can recognize HLA molecules in the absence of bound peptides,25well-described examples of murine cross-reactive T cells document the importance of both nonself major histocompatibility complex (MHC) and peptide.26 At this time, the molecular identity of the peptide or peptides bound to HLA B44 or 45 and recognized by HSV-2–reactive CD8 are not known. The peptide(s) is likely to have a broad tissue distribution, as both B cells and renal epithelium–derived cells are reactive, and to be conserved between African green monkeys and humans. Several predictions based on our findings could be tested in further investigations. PBMCs from A*0201/B44 persons infected with HSV-2 ought not to give rise to B44-specific alloreactive T cells after in vitro restimulation with HSV-2 peptide. We would also predict that allogeneic stimulation of PBMCs from A*0201-bearing donors by B44-bearing cells would result in CTLs with activity against A*0201-infected cells sensitized by HSV-2 infection or HSV-2 peptides. Positive results from such a reciprocal experiment have been reported in defined EBV systems.31 Our laboratory plans to address these predictions in future experiments.

Our observations may have clinical consequences in 2 distinct clinical scenarios. In the first scenario, hematopoietic stem cells and/or naive or T cells are transplanted into a HLA A*0201– and HLA B*44–bearing recipient. Antibodies to KSHV were measured in filter paper eluates using an ELISA for the envelope glycoprotein K8.1 (lytic antibodies) and an immunofluorescence assay for latency-associated nuclear antigen (LANA)-1 (latent antibodies), as described elsewhere [11]. Itching, burning or tingling may occur just before the sores develop. In other words, the physiological state of living cells has a significant effect on the outcome of the virus infection, since the host cell provides the synthetic machinery, key regulatory molecules, and precursors for the newly synthesized viral proteins and nucleic acids. After 48 h, the medium was removed and cells were fixed for 2 min using 5% (vol/vol) formalin in water. These observations suggest that KSHV can sense and respond to changes in its host cell in previously unappreciated ways that should confer a strong advantage to a virus.

hepatitis G virus (HGV) a parenterally transmitted flavivirus originally isolated from a patient with chronic hepatitis; most infections are benign, and it is uncertain what role, if any, HGV plays in the etiology of liver disease. We thank Sigrid N. For example, binding of HSV-1 gD to the surface receptor nectin-1 (a member of the immunoglobulin superfamily and also known as HveC and CD111) stimulates Rho GTPase signaling, which in turn can alter the morphology of cortical actin. The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.