Replication of Herpes Simplex Virus in Human T Lymphocytes

Teute, H.; Braun, Rüdiger W.; Kirchner, Holger; Becker, H; Münk, K.

doi:10.1159/000149371

Cited by 27 publications

(22 citation statements)

References 20 publications

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“…Only 8-18 % of the hypodiploid fractions of PHA-treated cells were positive for antigen expression, in contrast to significantly greater proportions (36-82 %) of the corresponding S-G2\M fractions. These data indicate that HSV-1 preferentially replicates in proliferating cells as previously reported (Teute et al, 1983 ;Braun et al, 1984), and also that apoptosis occurs in cells not expressing detectable HSV-1 antigen.…”

supporting

confidence: 88%

Apoptosis of cord blood T lymphocytes by herpes simplex virus type 1.

Ito

Koide²,

Watanabe³

et al. 1997

Journal of General Virology

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We investigated apoptosis induced by herpes simplex virus type 1 (HSV-1) in cord blood T lymphocytes by using agarose gel electrophoresis, DNA content analysis and the terminal deoxytransferase (TdT)-mediated dUTP nick end-labelling (TUNEL) method. DNA fragmentation and the hypodiploid fraction in the cell cycle were both increased in HSV-1-infected CD4 and CD8 lymphocytes stimulated with phytohaemagglutinin (PHA) compared to mock-infected lymphocytes. The percentage of cells in the S phase was decreased in HSV-1-infected CD4 and CD8 lymphocytes. HSV-1 antigen, glycoprotein D (gD) and regulatory protein ICP27 were detected in 8-18 % of the hypodiploid fraction of PHA-stimulated, HSV-1-infected lymphocytes. Apoptosis was induced not only in HSV-1 antigenexpressing cells but also in cells not expressing detectable viral proteins. Addition of anti-Fas antibody, anti-Fas-ligand antibody or a mixture of both had no effect on HSV-1-induced apoptosis, indicating that the Fas-Fas-ligand pathway did not contribute to HSV-1-induced apoptosis.Herpes simplex virus (HSV) causes severe infection with high mortality in human neonates (Whitley et al., 1991). The low frequency of specific T lymphocytes responding to HSV at birth is thought to be responsible for the severity of primary HSV infection in neonates (Hayward et al., 1984). Human herpesviruses, such as HSV-1 (Tropea et al., 1995), varicellazoster virus (Sadzot-Delvaux et al., 1995) and Epstein-Barr virus (EBV ; Kawanishi et al., 1993), induce apoptosis. In addition virus-induced apoptosis of lymphoid cells may be a major cause of immunosuppression (Groux et al., 1992 ;Razvi et al., 1993). The effect of HSV-1 infection on lymphocytes from neonates has not been fully investigated. In this study, we have investigated the induction of apoptosis by HSV-1 in T Author for correspondence : Masahiro Ito.Fax j81 59 231 5213. e-mail virus!clin.medic.mie-u.ac.jp lymphocytes from neonates and the relationship between apoptosis and impaired immune function.HSV-1 (KOS strain) was grown at an m.o.i. of 0n1 in Vero cells that were cultured in minimum essential medium (MEM, Gibco BRL) supplemented with 10 % foetal bovine serum (FBS, Gibco BRL) at 37 mC. After 48 h, the supernatant was collected and cell debris was removed by centrifugation. The supernatant virus stock was stored at k70 mC. The titre of HSV-1 in the virus stock was 2i10' p.f.u.\ml. Supernatant medium from uninfected Vero cells was used for mock-infected controls.Cord blood was obtained from the placental end of the cord at full-term birth, and mononuclear cells (MNC) were separated by Ficoll-Hypaque (Histopaque 1077, Sigma) gradient centrifugation. MNC at the interface were collected and washed three times with RPMI-1640 (Gibco BRL) and suspended in RPMI-1640 supplemented with 10 % FBS. CD4-and CD8-rich lymphocytes were obtained by using Dynabeads M-450 CD4 and M-450 CD8 (Dynal). These procedures resulted in yields of 95 % CD4 and CD8 cells.Lymphocytes (1i10' cells) were centrifuged at 1500 r.p.m. for 5 min. The pellete...

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supporting

confidence: 88%

Apoptosis of cord blood T lymphocytes by herpes simplex virus type 1.

Ito

Koide²,

Watanabe³

et al. 1997

Journal of General Virology

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“…Although apoptosis of infected cells is usually efficiently inhibited by HSV-1, its contribution to the decrease in cell viability should not be discounted, as the inhibitory effect is highly species and cell type specific (15,21). This represents the first demonstration of productive HSV infection of DC, and it contrasts with those reported for freshly isolated peripheral blood monocytes and lymphocytes, which are innately resistant to HSV infection (2,44,48). In the latter cells, viral replication is inhibited early in the replicative cycle prior to immediate-early protein synthesis and no viral DNA synthesis is detectable.…”

Section: Discussioncontrasting

confidence: 60%

Immature Monocyte-Derived Dendritic Cells Are Productively Infected with Herpes Simplex Virus Type 1

Mikloška

Bošnjak

Cunningham

2001

J Virol

158

191

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Herpes simplex virus type 1 (HSV-1) initially infects epidermal or mucosal tissues where it replicates and enters the cutaneous sensory axons. It is then retrogradely transported to the neurons of dorsal root ganglia where latent infection is established. Sporadic reactivation of latent virus and transmission to peripheral sites leads to asymptomatic viral shedding or recurrent herpes lesions (41, 50). Symptomatic recurrences are dependent on the levels of local immunity at the periphery and are principally controlled by cell-mediated responses via direct T-cell effector function and cytokine release (24,34,37,45). CD4 ϩ T cells are the initial infiltrating cells in the recurrent lesion, followed by CD8 ϩ cells (9). An immediate-early gene product, ICP47, inhibits major histocompatibility complex (MHC) class I-mediated antigen presentation by binding via its N terminus to the transporter-associated protein (TAP) (1,13,18,49,52). This ICP47-TAP complex prevents translocation of the MHC class I-processed peptide complex to the cell surface, which would prevent recognition by CD8 ϩ T cells. However, gamma interferon secreted by CD4 cells reverses the MHC class I downregulation and stimulates MHC class II expression, allowing targeting of HSV-infected epidermal cells by both CD4 ϩ and CD8 ϩ cytotoxic T cells (33). The persistence of HSV-specific CD8 ϩ clones in seropositive individuals, however, suggests their complementary importance to CD4 ϩ T cells in the control of recurrences (35, 36). The early appearance of virus-specific T-cell effectors depends on prompt signaling from antigen-presenting cells, such as dendritic cells (DC), B cells, or macrophages. The strategic positioning of Langerhans cells in the skin and mucosa identifies them as the most likely antigen-presenting DC to have the earliest contact with the incoming virus.DC form a network of bone marrow-derived antigen-presenting cells that are required for the initiation of adaptive immune responses. DC can be found in virtually all peripheral tissues and are characterized by the CD1a ϩ HLA-DR ϩ CD80 ϩ CD86 ϩ phenotype (3, 17). The capacity of DC to stimulate T cells is closely related to their maturation stage (40). Immature DC, exemplified by epidermal Langerhans cells, act as sentinels and are highly specialized at antigen uptake and processing but are poor stimulators of primary immune responses (3,17,43). A variety of immune stimuli induce phenotypic and functional changes to resting DC as they migrate out of the tissues and into secondary lymphoid organs. Mature DC no longer take up and process antigen but upregulate MHC class I and II costimulatory and adhesion molecules, effectively boosting their ability to present processed peptides to antigen-specific T cells. During the process of maturation, DC also express CD83, a maturation marker not found on resting immature DC such as Langerhans cells (54). Terminal maturation of DC is induced upon contact with T cells via CD40 ligation (6). Experimental studies of human Langerhans cells have been hamp...

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“…This increase in latency after Flt3L immunization or CD11c ϩ CD8␣ ϩ transfer is not due to higher-level infection of DCs, since DCs are resistant to HSV-1 replication (1,49,61,68).…”

Section: Cd8␣mentioning

confidence: 93%