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D C Johnson

Publications and source records attributed to D C Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1999

2-methoxyestradiol-induced growth suppression and lethality in estrogen-responsive MCF-7 cells may be mediated by down regulation of p34cdc2 and cyclin B1 expression.

MCF-7 breast cancer cells increase their rate of proliferation, as indicated by incorporation of tritiated thymidine into DNA, when exposed to estrogen. In confirmation of other studies, 10 nM 17beta-estradiol (E2) increased proliferation by 2.8-fold after 6 days of exposure. As indicated by trypan blue exclusion and TUNEL assays, cell survival was increased and apoptosis decreased by the presence of E2. The estradiol metabolite 2-methoxyestradiol (2-ME) when present in the culture medium in concentrations greater than 1 microM for three days, dose-dependently reduced the effectiveness of E2 on cell proliferation by increasing the rate of apoptosis. To examine a mechanism for the increase in apoptosis, expression of p34cdc2 and cyclin B1 protein levels were monitored by examination of immunoblots of their proteins. E2 increased p34cdc2 and cyclin B1 protein levels significantly after 6 days of exposure. This effect was inhibited significantly by the presence of 2-ME. The results indicate that up-regulation of p34cdc2 and cyclin B1 is closely associated with increased survivability and lack of apoptosis in estrogen-induced proliferation of MCF-7 cells. Further, anti-estrogenic effects of 2-ME in these cells can be accounted for by its activation of apoptotic functions, which are correlated with reductions in expression of p34cdc2 and cyclin B1 genes.

2-Methoxyestradiol↗
PubMed1998

Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response.

The herpes simplex virus (HSV) infected cell protein (ICP)47 blocks CD8+ T cell recognition of infected cells by inhibiting the transporter associated with antigen presentation (TAP). In vivo, HSV-1 replicates in two distinct tissues: in epithelial mucosa or epidermis, where the virus enters sensory neurons; and in the peripheral and central nervous system, where acute and subsequently latent infections occur. Here, we show that an HSV-1 ICP47- mutant is less neurovirulent than wild-type HSV-1 in mice, but replicates normally in epithelial tissues. The reduced neurovirulence of the ICP47- mutant was due to a protective CD8+ T cell response. When compared with wild-type virus, the ICP47- mutant expressed reduced neurovirulence in immunologically normal mice, and T cell-deficient nude mice after reconstitution with CD8+ T cells. However, the ICP47- mutant exhibited normal neurovirulence in mice that were acutely depleted of CD8+ T cells, and in nude mice that were not reconstituted, or were reconstituted with CD4+ T cells. In contrast, CD8+ T cell depletion did not increase the neurovirulence of an unrelated, attenuated HSV-1 glycoprotein (g)E- mutant. ICP47 is the first viral protein shown to influence neurovirulence by inhibiting CD8+ T cell protection.

Animals↗
PubMed1998

An experimental model of small intestinal submucosa as a growing vascular graft.

OBJECTIVE: The ideal vascular graft for use in children with congenital heart disease should not only be biocompatible and nonthrombogenic and present no infectious risk, but ideally it should grow at the same rate as the recipient. METHODS: We have tested autologous small intestine submucosa as a superior vena cava interposition graft in 11 piglets. The grafts were prepared from segments of jejunum, rendered nonthrombogenic by heparin bonding. The superior vena cava from the level of the azygos vein to the superior vena cava-right atrial junction was replaced. RESULTS: One early and 1 late death were not related to the graft material. At 90 days, the weight of the 9 survivors increased by 630%, from a mean of 10.3 +/- 2.0 kg to a mean of 59.2 +/- 16.7 kg (P < .001). The grafts increased in circumference by 184%, from a mean of 36.8 +/- 4.4 mm to a mean of 61.4 +/- 12.1 mm (P < .001) at late follow-up. Their length increased by 147%, from a mean of 9.9 +/- 2.1 mm at implantation to a mean of 15.8 +/- 5.5 mm at explantation (P = .002 ). At the time of explantation, all 11 grafts were patent and free of thrombus. Cavograms showed no anastomotic stricture or aneurysm formation in 7 of 9 cases. The luminal surface of all grafts was smooth, shiny, and indistinguishable from that of the native cava. Light microscopy showed a loosely textured collagen framework, with a dense capillary network and complete luminal coverage by a single, continuous cell layer displaying the ultrastructural features characteristic of endothelial cells. CONCLUSION: Small intestine submucosa provides a collagen framework that becomes remodeled, grows, and acquires a nonthrombogenic endothelial lining. This makes it potentially well suited as a cardiovascular substitute in children.

Animals↗
PubMed1998

The herpes simplex virus gE-gI complex facilitates cell-to-cell spread and binds to components of cell junctions.

The herpes simplex virus (HSV) glycoprotein complex gE-gI mediates the spread of viruses between adjacent cells, and this property is especially evident for cells that form extensive cell junctions, e.g., epithelial cells, fibroblasts, and neurons. Mutants lacking gE or gI are not compromised in their ability to enter cells as extracellular viruses. Therefore, gE-gI functions specifically in the movement of virus across cell-cell contacts and, as such, provides a molecular handle on this poorly understood process. We expressed gE-gI in human epithelial cells by using replication-defective adenovirus (Ad) vectors. gE-gI accumulated at lateral surfaces of the epithelial cells, colocalizing with the adherens junction protein beta-catenin but was not found on either the apical or basal plasma membranes and did not colocalize with ZO-1, a component of tight junctions. In subconfluent monolayers, gE-gI was found at cell junctions but was absent from those lateral surfaces not in contact with another cell, as was the case for beta-catenin. Similar localization of gE-gI to cell junctions was observed in HSV-infected epithelial cells. By contrast, HSV glycoprotein gD, expressed using a recombinant Ad vectors, was found primarily along the apical surfaces of cells, with little or no protein found on the basal or lateral surfaces. Expression of gE-gI without other HSV polypeptides did not cause redistribution of either ZO-1 or beta-catenin or alter tight-junction functions. Together these results support a model in which gE-gI accumulates at sites of cell-cell contact by interacting with junctional components. We hypothesize that gE-gI mediates transfer of HSV across cell junctions by virtue of these interactions with cell junction components.

Adenoviruses, Human↗
PubMed1998

Herpes simplex virus type 2 ICP47 inhibits human TAP but not mouse TAP.

Herpes simplex virus serotype 1 (HSV-1) expresses an immediate-early protein, ICP47, that effectively blocks the major histocompatibility complex class I antigen presentation pathway. HSV-1 ICP47 (ICP47-1) binds with high affinity to the human transporter associated with antigen presentation (TAP) and blocks the binding of antigenic peptides. HSV type 2 (HSV-2) ICP47 (ICP47-2) has only 42% amino acid sequence identity with ICP47-1. Here, we compared the levels of inhibition of human and murine TAP, expressed in insect cell microsomes, by ICP47-1 and ICP47-2. Both proteins inhibited human TAP at similar concentrations, and the K(D) for ICP47-2 binding to human TAP was 4.8 x 10(-8) M, virtually identical to that measured for ICP47-1 (5.2 x 10(-8) M). There was some inhibition of murine TAP by both ICP47-2 and ICP47-1, but this inhibition was incomplete and only at ICP47 concentrations 50 to 100 times that required to inhibit human TAP. Lack of inhibition of murine TAP by ICP47-1 and ICP47-2 could be explained by an inability of both proteins to bind to murine TAP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Herpes simplex virus gD and virions accumulate in endosomes by mannose 6-phosphate-dependent and -independent mechanisms.

Herpes simplex virus (HSV) glycoprotein D (gD) is modified with mannose 6-phosphate (M6P) and binds to M6P receptors (MPRs). MPRs are involved in the well-characterized pathway by which lysosomal enzymes are directed to lysosomes via a network of endosomal membranes. Based on the impaired ability of HSV to form plaques under conditions in which glycoproteins could not interact with MPRs, we proposed that MPRs may function during HSV egress or cell-to-cell spread (C. R. Brunetti, R. L. Burke, B. Hoflack, T. Ludwig, K. S. Dingwell, and D. C. Johnson, J. Virol. 69:3517-3528, 1995). To further analyze M6P modification and intracellular trafficking of gD in the absence of other HSV proteins, adenovirus (Ad) vectors were used to express soluble and membrane-anchored forms of gD. Both membrane-bound and soluble gD were modified with M6P residues and were localized to endosomes that contained the 275-kDa MPR or the transferrin receptor. Similar results were observed in HSV-infected cells. Cell fractionation experiments showed that gD was not present in lysosomes. However, a mutant form of gD and another HSV glycoprotein, gI, that were not modified with M6P were also found in endosomes in HSV-infected cells. Moreover, a substantial fraction of the HSV nucleocapsid protein VP6 was found in endosomes, consistent with accumulation of virions in an endosomal compartment. Therefore, it appears that HSV glycoproteins and virions are directed to endosomes, by M6P-dependent as well as by M6P-independent mechanisms, either as part of the virus egress pathway or by endocytosis from the cell surface.

Adenoviridae↗
PubMed1998

Inhibition of major histocompatibility complex class I antigen presentation in pig and primate cells by herpes simplex virus type 1 and 2 ICP47.

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) express an immediate-early protein, ICP47, that effectively inhibits the human transporter associated with antigen presentation (TAP), blocking major histocompatibility complex (MHC) class I antigen presentation to CD8+ T cells. Previous work indicated that the mouse TAP is relatively resistant to inhibition by the HSV-1 and HSV-2 ICP47 proteins (ICP47-1 and ICP47-2) and that mouse cells infected with HSV-1 are lysed by anti-HSV CD8+ cytotoxic T lymphocytes (CTL). Therefore, mice are apparently not suitable animals in which to study the in vivo effects of ICP47. In order to find an animal model, we introduced ICP47-1 and ICP47-2 into cells from various animal species-mice, rats, guinea pigs, rabbits, dogs, pigs, cows, monkeys, and humans-and measured TAP activity in the cells. Both proteins were unable to inhibit TAP in mouse, rat, guinea pig, and rabbit cells. In contrast, ICP47-1 and ICP47-2 inhibited TAP in pig, dog, cow, and monkey cells, and the TAP in pig and dog fibroblasts was often more sensitive to both proteins than TAP in human fibroblasts. These results were extended by measuring CD8+-T-cell recognition (CTL lysis) of cells from various species. Cells were infected with recombinant HSV-1 constructed to express murine MHC class I proteins so that the cells would be recognized and lysed by well-characterized murine anti-HSV CTL unless antigen presentation was blocked by ICP47. Anti-HSV CD8+ CTL effectively lysed pig and primate cells infected with a recombinant HSV-1 ICP47- mutant but were unable to lyse pig or primate cells infected with a recombinant HSV-1 that expressed ICP47. Therefore, pigs, dogs, and monkeys may be useful animal models in which to test the effects of ICP47 on HSV pathogenesis or the use of ICP47 as a selective immunosuppressive agent.

Animals↗
PubMed1998

Differential spatiotemporal regulation of lactoferrin and progesterone receptor genes in the mouse uterus by primary estrogen, catechol estrogen, and xenoestrogen.

Many xenobiotics are considered reproductive toxins because of their ability to interact with the nuclear estrogen receptors (ERalpha and ERbeta). However, there is evidence that these xenobiotics can regulate gene expression in the reproductive targets by mechanisms that do not involve these ERs. To examine this further, we compared the effects of estrogenic (o,p'-DDT [1-(o-chlorophenyl)-1-(p-chlorophenyl)2,2,2-trichloroethane] and Kepone, chlordecone) and nonestrogenic (p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], a metabolite of p,p'-DDT) xenobiotics with those of 17beta-estradiol (E2) and 4-hydroxyestradiol-17beta (4-OH-E2), a catechol metabolite of E2, on uterine expression of lactoferrin (LF) and progesterone receptor (PR). These genes are estrogen responsive in the mouse uterus. Normally, LF is expressed in the uterine epithelium, whereas PR is expressed in both the epithelium and stroma in response to estrogenic stimulation. Ovariectomized mice were injected with xenobiotics (7.5 mg/kg), E2 (10 microg/kg), 4-OH-E2 (10 microg/kg), or the vehicle (oil, 0.1 ml/mouse), and uterine tissues were processed for Northern blot and in situ hybridization. The pure antiestrogen ICI-182780 (ICI; 1 or 20 mg/kg) was used to interfere with estrogenic responses that were associated with the ERs. The results of Northern and in situ hybridization demonstrated increased uterine levels of PR and LF messenger RNAs (mRNAs) by all of these xenobiotics, but quantitatively the responses were much lower than those induced by E2 or 4-OH-E2. The results further showed that the E2-inducible epithelial LF mRNA accumulation was markedly abrogated by pretreatment with ICI (20 mg/kg). In contrast, this treatment retained the epithelial expression of PR mRNA, but down-regulated the stromal expression. In contrast, ICI had negligible effects on LF and PR mRNA responses to 4-OH-E2, indicating that this catechol estrogen exerted its effects primarily via a mechanism(s) other than the ERs. The heightened accumulation of LF mRNA in the epithelium in response to Kepone and o,p'-DDT was also severely compromised by pretreatment with ICI, but this antiestrogen had little effect on responses to p,p'-DDD. Similar to E2, Kepone increased the expression of PR mRNA in both uterine epithelium and stroma. However, pretreatment with ICI decreased stromal cell expression, whereas epithelial cell expression remained unaltered or increased. These responses were not noted in mice treated with o,p'-DDT or p,p'-DDD. Collectively, the results demonstrate that catechol estrogens or xenobiotics can alter uterine expression of estrogen-responsive genes by mechanisms that are not totally mediated by the classical nuclear ERs, and these alterations are cell type specific. We conclude that an interaction of a compound with the nuclear ERalpha and/or ERbeta is not an absolute requirement for producing specific estrogen-like effects in the reproductive target tissues.

Animals↗
PubMed1997

The central respiratory effects of acetylcholine vary with CSF pH.

Hydrogen ion concentration [H+] centrally is a major determinant of ventilation. Its action involves central cholinergic mechanisms. The point(s) where increased [H+] induces its changes in the cholinergic system is unclear. If H+ acts presynaptically by increasing endogenous ACh synthesis and release, its effect should be absent when ACh is supplied exogenously. If H+ acts postsynaptically by changing ACh degradation or ACh receptor sensitivity, its effect should persist in the presence of exogenous ACh. We perfused the brain ventricular system in spontaneously breathing anesthetized dogs with progressively higher concentrations of ACh (0-52.8 mM) in cerebrospinal fluid (CSF) at pH 7.4 and CSF pH 7.1. Increasing concentrations of ACh increased ventilation > 4-fold in a linear manner in the presence of non-acidic and acidic CSF. With acidic CSF the ACh ventilatory response line was shifted to a higher y-intercept, resulting in a higher ventilation at any [ACh]. These findings are consistent with the hypothesis that central acidosis augments ventilation by postsynaptic cholinergic events.

Acetylcholine↗
PubMed1997

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases release of luteinizing hormone and follicle-stimulating hormone from the pituitary of immature female rats in vivo and in vitro.

Recent findings that serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were dramatically increased in weanling female Sprague-Dawley (S-D) rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prompted a more detailed study to define the effect and to investigate its mechanism(s). Dose-response and time-course studies were performed in vivo. Single doses (0.03-30 micrograms/kg) of TCDD were administered orally by gastric intubation to 22-day-old female rats. Control animals received vehicle (corn oil) only, whereas naive controls were treated with an empty intubation syringe. Trunk blood was collected after decapitation at various time points during the subsequent 72 hr. Concentrations of LH and FSH were determined in serum by radioimmunoassays (RIA). Two distinct peaks of both hormones were detected. The first, at 1 hr, appeared to be a non-specific response to vehicle as it was present in both vehicle control and TCDD-treated animals, but not in naive control animals. The second peak, at 24 hr, occurred only in animals dosed with TCDD. Gonadotropin levels in these animals were dose-dependently elevated. The ED50 was about 5 micrograms/kg with a maximum elevation of 15- and 20-fold for LH and FSH, respectively. Subsequently, in vitro studies were conducted in cultured pituitary halves and in primary pituitary cell cultures exposed to gonadotropin releasing hormone (GnRH) and/or TCDD. The amount of LH released into the media was measured by RIA. TCDD caused a dose-dependent release of LH from pituitary halves with an ED50 of about 0.1 nM. This effect was abolished in calcium-free medium but was not attenuated by an GnRH antagonist. Further in vitro studies were conducted in primary pituitary cell cultures. Although the cells responded to GnRH very well, no effect of up to 100 nM TCDD on the release of gonadotropins was detected. The results suggest that TCDD induces dose-dependently a brief release of gonadotropins in immature female rats. This effect is at least partially due to an effect of TCDD in the pituitary. Increased release of gonadotropins as a result of TCDD treatment depends on the action of calcium but does not occur via activation of GnRH receptors. However, cells in a primary pituitary culture do not respond to TCDD with increased release of gonadotropins, suggesting that the effect of TCDD in the pituitary is mediated by a factor present in pituitary halves but not in primary cell culture.

Administration, Oral↗
PubMed1997

Microprocessor based spatial TENS (transcutaneous electric nerve stimulator) designed with waveform optimality for clinical evaluation in a pain study.

A microprocessor based TENS device is developed which utilizes a spatial procedure in the administration of electrical fields to actively interfere with pain signals reaching the brain. This unusual design also has the advantage of requiring the frequency characteristics of the electrical waveform produced to be optimally tuned to the mechanical impedance properties of the skin/tissue. Hence a much more efficient procedure for the transfer of electrical energy from the TENS device to the human tissue is provided. Data are presented involving patients from the Dayton VA Medical Center in Ohio, USA being tested with this new microprocessor system compared to the treatment obtained via a traditional stimulator.

Adult↗
PubMed1997

Pneumonic tularemia in a patient with chronic granulomatous disease.

We report the case of a 14-year-old boy with granulomatous pneumonia caused by Francisella tularensis. In addition, an autosomal recessive form of chronic granulomatous disease was diagnosed. Both F. tularensis and chronic granulomatous disease are associated with pulmonary granulomas. To our knowledge, this is the first report of F. tularensis infection in a patient with chronic granulomatous disease. The relationship between these two processes is discussed.

Adolescent↗
PubMed1997

Preoperative predictors of operative morbidity and mortality in COPD patients undergoing bilateral lung volume reduction surgery.

Bilateral volume reduction surgery (VRS) improves lung function for selected patients with emphysema. However, predictors of outcome are not well defined. We reviewed the preoperative characteristics of the first 47 consecutive patients who underwent bilateral VRS at the Massachusetts General Hospital in order to define potential predictors of unacceptable outcome. Preoperative data included spirometry, plethysmography, diffusion of carbon monoxide (Dco), maximum inspiratory pressure (MIP), maximum expiratory pressure, resting arterial blood gases (ABG), cardiopulmonary exercise testing with ABG and lactate sampling, and radionuclide ventriculography. Prepulmonary and postpulmonary rehabilitation 6-min walk tets (6MWT), and preoperative chest CT scans were also obtained. Twenty-two subjects were male and 17 of the subjects were on the lung transplant list. Patient characteristics included age of 60.5 +/- 7.5 years, FEV1 of 0.67 +/- 0.20 L, total lung capacity of 7.56 +/- 1.7 L, Dco of 7.40 +/- 4.1 mL/min/mm Hg, and PaCO2 of 41.6 +/- 6.4 mm Hg (mean +/- SD). The FEV1, vital capacity, MIP, resting room air PaCO2, prepulmonary and postpulmonary rehabilitation 6MWT, and PaCO2 at maximum oxygen consumption correlated with length of hospitalization (p < 0.05). Based on analysis of 41 of 47 patients for whom there were complete data, the inability to walk more than 200 m on the 6MWT before or after preoperative pulmonary rehabilitation, and resting PaCO2 > or = 45 mm Hg were the best predictors of an unacceptable outcome. If either of these characteristics was present, six of 16 vs zero of 25 died (Fisher's Exact Test, p = 0.0025, one-tailed) and 11 of 16 vs four of 25 had hospital courses > 21 days (p < 0.002). Both the 6MWT < 200 m and resting PaCO2 > or = 45 mm Hg alone correlated with death (p = 0.004 and p = 0.012, respectively) and the resting PaCO2 > or = 45 mm Hg correlated with hospital days > 21 (p = 0.0002). In conclusion, the data suggest that the inability to walk at least 200 m in 6 min before or after pulmonary rehabilitation and a resting room air PaCO2 > or = 45 mm Hg are excellent preoperative predictors of unacceptable postoperative outcomes.

Exercise Test↗
PubMed1997

Efficacy of iodine water purification tablets against Cryptosporidium oocysts and Giardia cysts.

The ability to control water-borne diseases is critical for soldiers, hikers, and others who may need to drink directly from an outdoor source. Water-borne protozoan parasites that are specifically of concern are Giardia and Cryptosporidium because of their resistance to halogen disinfection. The purpose of this study was to determine the effectiveness of iodine tablets against Giardia and Cryptosporidium under general- and worst-case water conditions that might be found in the field. Giardia cysts and Cryptosporidium oocysts were exposed to iodine according to manufacturer's instructions (two tablets/L = 13-18 mg/L for 20 minutes). This dose inactivated 3-log10 of Giardia in general-case water and pH 9. In worst-case water, however, only about 35% of cysts were inactivated at pH 5. Fifty minutes were required to achieve a 3-log10 reduction at pH 5. Cryptosporidium oocysts were more difficult to inactivate. Only 10% were inactivated after a 20-minute exposure to iodine according to manufacturer's instructions; even after 240 minutes of exposure to iodine only 66-81% oocysts were inactivated. These data strongly suggest that iodine disinfection is not effective in inactivating Cryptosporidium oocysts in water. Because this organism is common in all surface waters, it is recommended that another method of treatment be used before ingestion.

Animals↗
PubMed1996

Stable binding of the herpes simplex virus ICP47 protein to the peptide binding site of TAP.

The herpes simplex virus (HSV) ICP47 protein inhibits the MHC class I antigen presentation pathway by inhibiting the transporter associated with antigen presentation (TAP) which translocates peptides across the endoplasmic reticulum membrane. At present, ICP47 is the only inhibitor of TAP. Here, we show that ICP47 produced in bacteria can block human, but not mouse, TAP, and that heat denaturation of ICP47 has no effect on its ability to block TAP. ICP47 inhibited peptide binding to TAP without affecting ATP binding, consistent with previous observations that the peptide binding and ATP binding sites of TAP are distinct. ICP47 bound to TAP with a higher affinity (KD approximately 5 x 10(-8) M) than did peptides, and ICP47 did not dissociate from TAP. ICP47 was not transported by TAP and remained sensitive to proteases added from the cytosolic surface of the membrane. Peptides acted as competitive inhibitors of ICP47 binding to TAP, and this inhibition required a 100- to 1000-fold molar excess of peptide. These results demonstrate that ICP47 binds to a site which includes the peptide binding domain of TAP and remains bound to this site in a stable fashion.

Adenosine Triphosphate↗
PubMed1996

Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2-infected fibroblasts after treatment with IFN-gamma or when virion host shutoff functions are disabled.

Herpes simplex virus (HSV)-specific CD8+ CTL cloned from individuals infected with HSV-2 efficiently lyse HSV-infected EBV-transformed B lymphoblastoid cells; however, these same CTL fail to lyse infected dermal fibroblasts. By 3 h after infection (early), class I MHC expression is reduced to less than 20% of that in uninfected fibroblasts, and expression is further reduced to less than 1% of the level in uninfected cells between 6 and 18 h after infection (late). We used an HSV-2 mutant that lacked the virion host shutoff (vhs) function to demonstrate that vhs plays a role in the loss of class I expression. While fibroblasts infected with this mutant are lysed by CTL that recognize virion proteins presented early as a consequence of introduction into the cytoplasm by the infecting virus, they are resistant to lysis by CTL that recognize viral proteins that must be synthesized de novo to be presented as class I Ags. Fibroblasts infected with a mutant that lacks the transporter-associated protein inhibitor ICP47 and is partially vhs defective are sensitive to CTL lysis. Pretreatment of fibroblasts with IFN-gamma prior to HSV infection sustained the level of class I expression for longer periods after infection, and these fibroblasts, infected with wild-type HSV-2, were partially sensitive to lysis by HSV-specific CTL. Taken together, these results suggest that the combined effects of the HSV-2 vhs and ICP47 gene products are to block Ag presentation by class I MHC. However, this effect can be transiently counteracted by IFN-gamma providing an early role for CD8+ CTL in the cellular immune response to HSV-2.

Antigen Presentation↗