Superior Electrochemical Performance of Pristine Nickel Hexaaminobenzene MOF Supercapacitors Fabricated by Electrophoretic Deposition.

2 D Metal-organic frameworks (MOFs) are promising materials for supercapacitor electrodes because of their controllable structure, tunable pore size, and high specific surface area. In this study, the fabrication of pristine MOF nickel hexaaminobenzene Ni3 (HAB)2 supercapacitor electrodes by electrophoretic deposition (EPD) was reported. The MOF-based symmetric supercapacitor demonstrated a superior electrochemical capacitive performance over a potential window of 0-1.0 V and displayed an areal capacitance of 13.64 mF cm-2 and a remarkable ultra-high cycling stability with a retention of 81 % over 50 000 cycles. The supercapacitor's outstanding performance was attributed to the binder-free EPD process and to the 2 D MOF nanosheets, which facilitate ion diffusion throughout the electrodes. These promising results demonstrate the potential of using pristine MOFs as the next generation of materials for energy-storage applications.

Sequence and comparative analysis of the genome of HSV-1 strain McKrae.

Ocular infection by HSV-1 strain McKrae is neurovirulent in both mice and rabbits and causes fatal encephalitis in approximately 50% of animals. In addition, it spontaneously reactivates with high frequency relative to other HSV-1 strains in rabbits. We sequenced the McKrae strain genome and compared its coding protein sequences with those of six other HSV-1 strains. Most of the 74 predicted protein sequences are conserved; only eleven are less than 98% conserved. Eight proteins were identified to be unique for McKrae based on sequence homology bit score ratio (BSR). These include five proteins showing significant variations (RL1, RS1, UL49A, US7 and US11), two truncated proteins (UL36 and UL56) and one (US10) containing an extended open reading frame. The McKrae strain also has unique features in its 'a' sequence and non-coding sequences, such as LAT and miRNA. These data are indicative of strain variation but need further work to connect observed differences with phenotype effects.

Cardiac Pathology in Glycogen Storage Disease Type III.

PURPOSE: To investigate the distribution and clinical impact of glycogen accumulation on heart structure and function in individuals with GSD III. METHODS: We examined cardiac tissue and the clinical records of three individuals with GSD IIIa who died or underwent cardiac transplantation. Of the two patients that died, one was from infection and the other was from sudden cardiac death. The third patient required cardiac transplantation for end-stage heart failure with severe hypertrophic cardiomyopathy. RESULTS: Macro- and microscopic examination revealed cardiac fibrosis (n = 1), moderate to severe vacuolation of cardiac myocytes (n = 3), mild to severe glycogen accumulation in the atrioventricular (AV) node (n = 3), and glycogen accumulation in smooth muscle cells of intramyocardial arteries associated with smooth muscle hyperplasia and profoundly thickened vascular walls (n = 1). CONCLUSION: Our findings document diffuse though variable involvement of cardiac structures in GSD III patients. Furthermore, our results also show a potential for serious arrhythmia and symptomatic heart failure in some GSD III patients, and this should be considered when managing this patient population.

A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge.

The next generation of needle-free mucosal vaccines is being rationally designed according to rules that govern the way in which the epitopes are recognized by and stimulate the genital mucosal immune system. We hypothesized that synthetic peptide epitopes extended with an agonist of Toll-like receptor 2 (TLR-2), that are abundantly expressed by dendritic and epithelial cells of the vaginal mucosa, would lead to induction of protective immunity against genital herpes. To test this hypothesis, we intravaginally (IVAG) immunized wild-type B6, TLR-2 (TLR2(-/-)) or myeloid differentiation factor 88 deficient (MyD88(-/-)) mice with a herpes simplex virus type 2 (HSV-2) CD8+ T-cell peptide epitope extended by a palmitic acid moiety (a TLR-2 agonist). IVAG delivery of the lipopeptide generated HSV-2-specific memory CD8+ cytotoxic T cells both locally in the genital tract draining lymph nodes and systemically in the spleen. Moreover, lipopeptide-immunized TLR2(-/-) and MyD88(-/-) mice developed significantly less HSV-specific CD8+ T-cell response, earlier death, faster disease progression, and higher vaginal HSV-2 titers compared to lipopeptide-immunized wild-type B6 mice. IVAG immunization with self-adjuvanting lipid-tailed peptides appears to be a novel mucosal vaccine approach, which has attractive practical and immunological features.

[Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in locally advanced nasopharyngeal carcinomas]. / Lokal fortgeschrittene Nasopharynxkarzinome. Hyperfraktioniert-akzelerierte Radiotherapie mit simultaner Chemotherapie.

BACKGROUND: The excellent results yielded by hyperfractionated and accelerated radiotherapy associated with concurrent chemotherapy in locally advanced oropharyngeal and hypopharyngeal carcinomas led to investigation of this therapeutic regimen in nasopharyngeal carcinomas also. METHODS: Thirty-five patients with stage III and IV nasopharyngeal carcinomas received accelerated hyperfractionated radiotherapy with concurrent chemotherapy (5-FU, mitomycin C + leucovorin). In the first 3 weeks of treatment five 2-Gy doses per week were delivered to the primary tumour and regional lymph nodes. The fractionation was then accelerated, with 1.4 Gy given twice daily until a total dose of 72 Gy had been administered. RESULTS: The overall objective response rate was 100%. The median follow-up period was 71 months. Salvage surgery of the lymph nodes was performed in 10 patients, revealing vital tumour tissue in 6 of these. The actuarial 5-year local control rate was 64% (95%CI: 47-81%), while overall actuarial survival at 5 years was 70% (95%CI: 53-86%). CONCLUSION: Hyperfractionated accelerated radiotherapy with concurrent chemotherapy is effective and feasible in locally advanced nasopharyngeal carcinoma.

Ventricular arrhythmia in the X-linked cardiomyopathy Barth syndrome.

Barth syndrome is an X-linked disorder characterized by dilated cardiomyopathy, cyclic neutropenia, skeletal myopathy, abnormal mitochondria, and growth deficiency. The primary defect is a mutation in the TAZ gene on the X chromosome at Xq28, resulting in abnormal phospholipid biosynthesis and cardiolipin deficiency. To date, there has been no systematic evaluation of the cardiac phenotype. We report five cases of cardiac arrest and/or placement of an internal cardiac defibrillator with documented ventricular arrhythmia. We suggest that ventricular arrhythmia is part of the primary phenotype of the disorder and that patients should be screened accordingly.

Mapping herpes simplex virus type 1 latency-associated transcript sequences that protect from apoptosis mediated by a plasmid expressing caspase-8.

LAT (latency-associated transcript) is the only herpes simplex virus type 1 (HSV-1) transcript abundantly expressed during neuronal latency. LAT expression is required for the high reactivation phenotype of HSV-1 and this phenotype correlates with LAT's anti-apoptosis properties. LAT nucleotides 1 to 1499 inhibit caspase-8 (death receptor apoptotic pathway), but not caspase-9 (mitochondrial apoptotic pathway), -induced apoptosis as efficiently as larger LAT fragments. LAT sequences important for inhibiting caspase-8-induced apoptosis were also localized. The ability of LAT nucleotides 1 to 1499 to efficiently inhibit caspase-8-induced apoptosis correlates with the high reactivation phenotype of a mutant virus expressing just the first 1.5 kb of LAT (nucleotides 1 to 1499).

Three herpes simplex virus type 1 latency-associated transcript mutants with distinct and asymmetric effects on virulence in mice compared with rabbits.

Herpes simplex virus type 1 latency-associated transcript (LAT)-null mutants have decreased reactivation but normal virulence in rabbits and mice. We report here on dLAT1.5, a mutant with LAT nucleotides 76 to 1667 deleted. Following ocular infection of rabbits, dLAT1.5 reactivated at a lower rate than its wild-type parent McKrae (6.1 versus 11.8%; P = 0.0025 [chi-square test]). Reactivation was restored in the marker-rescued virus dLAT1.5R (12.6%; P = 0.53 versus wild type), confirming the importance of the deleted region in spontaneous reactivation. Compared with wild-type or marker-rescued virus, dLAT1.5 had similar or slightly reduced virulence in rabbits (based on survival following ocular infection). In contrast, in mice, dLAT1.5 had increased virulence (P < 0.0001). Thus, deletion of LAT nucleotides 76 to 1667 increased viral virulence in mice but not in rabbits. In contrast, we also report here that LAT2.9A, a LAT mutant that we previously reported to have increased virulence in rabbits (G. C. Perng, S. M. Slanina, A. Yuhkt, B. S. Drolet, W. J. Keleher, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 73:920-929, 1999), had decreased virulence in mice (P = 0.03). In addition, we also found that dLAT371, a LAT mutant that we previously reported to have wild-type virulence in rabbits (G. C. Perng, S. M. Slanina, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 70:2014-2018, 1996), had decreased virulence in mice (P < 0.05). Thus, these three mutants, each of which encodes a different LAT RNA, have different virulence phenotypes. dLAT1.5 had wild-type virulence in rabbits but increased virulence in mice. In contrast, LAT2.9A had increased virulence in rabbits but decreased virulence in mice, and dLAT371 had wild-type virulence in rabbits but decreased virulence in mice. Taken together, these results suggest that (i) the 5' end of LAT and/or a gene that overlaps part of this region is involved in viral virulence, (ii) this virulence appears to have species-specific effects, and (iii) regulation of this virulence may be complex.

Recombinant herpes simplex virus type 1 expressing murine interleukin-4 is less virulent than wild-type virus in mice.

The effect of interleukin-4 (IL-4) on herpes simplex virus type 1 (HSV-1) infection in mice was evaluated by construction of a recombinant HSV-1 expressing the gene for murine IL-4 in place of the latency-associated transcript (LAT). The mutant virus (HSV-IL-4) expressed high levels of IL-4 in cultured cells. The replication of HSV-IL-4 in tissue culture and in trigeminal ganglia was similar to that of wild-type virus. In contrast, HSV-IL-4 appeared to replicate less well in mouse eyes and brains. Although BALB/c mice are highly susceptible to HSV-1 infection, ocular infection with HSV-IL-4 resulted in 100% survival. Furthermore, 57% of the mice survived coinfection with a mixture of HSV-IL-4 and a lethal dose of wild-type McKrae, compared with only 10% survival following infection with McKrae alone. Similar to wild-type BALB/c mice, 100% of IL-4(-/-) mice also survived HSV-IL-4 infection. T-cell depletion studies suggested that protection against HSV-IL-4 infection was mediated by a CD4(+)-T-cell response.

A herpes simplex virus type 1 mutant deleted for gamma34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation.

To create an oncolytic herpes simplex virus type 1 (HSV-1) that is inhibited for reactivation, we constructed a novel herpes recombinant virus with deletions in the gamma34.5 and LAT genes. The LAT gene was replaced by the gene for green fluorescent protein, thereby allowing viral infection to be followed. This virus, designated DM33, is effective in killing primary and established human glioma cell lines in culture. DM33 is considerably less virulent following intracerebral inoculation of HSV-susceptible BALB/c mice than the wild-type HSV-1 strain McKrae. The safety of this virus is further supported by the retention of its sensitivity to ganciclovir and its relatively limited toxicity against cultured human neuronal cells, astrocytes, and endothelial cells. The ability of DM33 to spontaneously reactivate was tested in a rabbit ocular infection model that accurately depicts human herpes infection and reactivation. Following ocular infection of rabbits, spontaneous reactivation was detected in 83% (15/18) of the eyes infected with wild-type McKrae. In contrast, none of the eyes infected with DM33 had detectable reactivation. The efficacy of this virus in cultured human glioma cell lines, its safety, confirmed by its inability to reactivate, and its attenuated neurovirulence make DM33 a promising oncolytic agent for tumor therapy.

Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture.

The latency-associated transcript (LAT) is the only abundant herpes simplex virus type 1 (HSV-1) transcript expressed during latency. In the rabbit eye model, LAT null mutants do not reactivate efficiently from latency. We recently demonstrated that the LAT null mutant dLAT2903 induces increased levels of apoptosis in trigeminal ganglia of infected rabbits compared to LAT+ strains (G.-C. Perng, C. Jones, J. Ciacci-Zarella, M. Stone, G. Henderson, A. Yokht, S. M. Slanina, F. M. Hoffman, H. Ghiasi, A. B. Nesburn, and C. S. Wechsler, Science 287:1500-1503, 2000). The same study also demonstrated that a plasmid expressing LAT nucleotides 301 to 2659 enhanced cell survival of transfected cells after induction of apoptosis. Consequently, we hypothesized that LAT enhances spontaneous reactivation in part, because it promotes survival of infected neurons. Here we report on the ability of plasmids expressing different portions of the 5' end of LAT to promote cell survival after induction of apoptosis. A plasmid expressing the first 1.5 kb of LAT (LAT nucleotides 1 to 1499) promoted cell survival in neuro-2A (mouse neuronal) and CV-1 (monkey fibroblast) cells. A plasmid expressing just the first 811 nucleotides of LAT promoted cell survival less efficiently. Plasmids expressing the first 661 nucleotides or less of LAT did not promote cell survival. We previously showed that a mutant expressing just the first 1.5 kb of LAT has wild-type spontaneous reactivation in rabbits, and a mutant expressing just the first 811 nucleotides of LAT has a reactivation frequency higher than that of dLAT2903 but lower than that of wild-type virus. In addition, mutants reported here for the first time, expressing just the first 661 or 76 nucleotides of LAT, had spontaneous reactivation indistinguishable from that of the LAT null mutant dLAT2903. In summary, these studies provide evidence that there is a functional relationship between the ability of LAT to promote cell survival and its ability to enhance spontaneous reactivation.

[Utilization of a new night vision enhancement device (DAVIS)]. / Einsatz einer neuen Nachtsichtbrille (DAVIS).

PATIENTS AND METHODS: Following complete ophthalmologic examination 37 patients with night blindness due to Retinitis Pigmentosa (sometimes Usher-Syndrome) and Choroideremia (n = 3) performed several tests with DAVIS during darkness. We evaluated the improvement of visual function on a special outside course in the city of Heidelberg (duration 1.5 to 4 hours). RESULTS: Twenty six of the patients were able to better recognize obstacles, 28 could see objects which were not seen without DAVIS. Twenty two of the 37 patients would use the DAVIS. Patients needed a visual acuity of more than 0.1 and more than 6 degree of central visual field to experience improvement with DAVIS. However, in patients with only minimal changes of the visual field, the restriction due to the presence of the device was a drawback. Sudden occurrence of light sources leads to blinding and limits the indoor use. CONCLUSION: DAVIS enhances contrast acuity especially during night and twilight. This leads to improvement of orientation due to better recognition of obstacles and allows rehabilitation of patients with night blindness for outdoor mobility. Individual test and adjustment of DAVIS is necessary to allow exact and adequate prescription.

Antibody-dependent enhancement of HSV-1 infection by anti-gK sera.

We previously reported that vaccination of BALB/c mice with the baculovirus expressed HSV-1 glycoprotein K (gK) or passive transfer of gK purified IgG to naive BALB/c mice causes severe exacerbation of HSV-1 induced corneal scarring following ocular challenge. In addition, a productive chronic infection, rather than a latent infection, is found in most trigeminal ganglia. These phenomena are accompanied by a very high T(H)1+T(H)2 response in the eye (Ghiasi, H., Cai, S., Nesburn, A.B., Wechsler, S.L., 1996. Vaccination with herpes simplex virus type 1 glycoprotein K impairs clearance of virus from the trigeminal ganglia resulting in chronic infection. Virology 224, 330-333; Ghiasi, H., Cai, S., Slanina, S., Nesburn, A. B., Wechsler, S.L., 1997. Nonneutralizing antibody against the glycoprotein K of herpes simplex virus type-1 exacerbates herpes simplex virus type-1-induced corneal scarring in various virus-mouse strain combinations. Invest. Ophthalmol. Vis. Sci. 38, 1213-1221; Ghiasi, H., Hofman, F.M., Cai, S., Perng, G.C., Nesburn, A.B., Wechsler, S.L., 1999. Vaccination with different HSV-1 glycoproteins induces different patterns of ocular cytokine responses following HSV-1 challenge of vaccinated mice. Vaccine 17, 2576-2582). In the studies reported here, we investigated the hypothesis that anti-gK serum produces antibody-dependent enhancement (ADE) of ocular HSV-1 infection. We found that gK vaccinated mice had significantly higher HSV-1 titers in their eyes than gD or mock-vaccinated mice and that anti-gK sera enhanced HSV-1 infection in the macrophage cell line U937. In addition, passive transfer of anti-gK sera to naive mice 24 h prior to ocular HSV-1 challenge also increased viral replication. These results were consistent with ADE of HSV-1 by sera to gK. This suggests that the severely exacerbated corneal disease seen following HSV-1 ocular challenge of gK vaccinated mice is a result of ADE. The ability of gK sera to cause harmful ADE may impact HSV-1 vaccine development.

The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection.

C57BL/6 mice depleted of NK (natural killer) cells with anti-asialo-GM1 antibody were more susceptible to lethal HSV-1 ocular challenge (12% survival) than control C57BL/6 mice (100% survival), CD4+ depleted mice (100% survival), CD8+ depleted mice (80% survival), or macrophage depleted mice (85% survival). NK depletion also resulted in significantly higher levels of HSV-1 induced corneal scarring than was seen with any of the other groups. C57BL/6 mice depleted of NK cells with PK136 (anti-NK1.1 antibody which is more specific for NK cells than is anti-asialo-GM1 antibody) were also more susceptible to HSV-1 ocular challenge than T cell or macrophage depleted mice. Vaccination completely protected NK depleted mice against death and corneal scarring. In contrast to C57BL/6 mice, in BALB/c mice, NK depletion had no effect on survival or corneal scarring following ocular HSV-1 challenge. Experiments with IFN-gamma knockout mice (IFN-gamma(o/o) mice) suggested that IFN-gamma played a minor role in protection of naïve mice against death following HSV-1 challenge. However, IFN-gamma did not appear to be an important factor in protection against HSV-1 induced eye disease. Thus, protection against HSV-1 induced corneal scarring in naive mice appeared to be due to a non-INF-gamma NK function. Our results therefore suggest that NK cells were very important in protecting naive C57BL/6 mice but not vaccinated C57BL/6 mice against corneal scarring and death following ocular HSV-1 challenge.

Both CD4+ and CD8+ T cells are involved in protection against HSV-1 induced corneal scarring.

AIM: To determine the relative impact of CD4+ T cells and CD8+ T cells in protecting mice against ocular HSV-1 challenge. METHODS: CD4+ T cell knockout mice (CD4-/- mice), CD8+ T cell knockout mice (CD8-/- mice), and mice depleted for CD4+ or CD8+ T cells by antibody (CD4+ depleted and CD8+ depleted mice), were examined for their ability to withstand HSV-1 ocular challenge. The parental mice for both knockout mice were C57BL/6J. RESULTS: These results suggest that: (1) both CD4+ deficient mice (CD4-/- and CD4+ depleted mice) and CD8+ deficient mice (CD8-/-, and CD8+ depleted mice) developed significantly more corneal scarring than their C57BL/6J parental strain; (2) the duration of virus clearance from the eyes of the CD4+ deficient mice was 4 days longer than that of the CD8+ deficient mice; and (3) the severity of corneal scarring in the CD4+ deficient mice was approximately twice that of the CD8+ deficient mice. CONCLUSIONS: It was reported here that: (1) CD4+ and CD8+ T cells were both involved in protection against lethal ocular HSV-1 infection; and (2) CD4+ and CD8+ T cells were both involved in protection against HSV-1 induced corneal scarring.

Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript.

Latent infections with periodic reactivation are a common outcome after acute infection with many viruses. The latency-associated transcript (LAT) gene is required for wild-type reactivation of herpes simplex virus (HSV). However, the underlying mechanisms remain unclear. In rabbit trigeminal ganglia, extensive apoptosis occurred with LAT(-) virus but not with LAT(+) viruses. In addition, a plasmid expressing LAT blocked apoptosis in cultured cells. Thus, LAT promotes neuronal survival after HSV-1 infection by reducing apoptosis.

The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits.

The latency-associated transcript (LAT) gene the only herpes simplex virus type 1 (HSV-1) gene abundantly transcribed during neuronal latency, is essential for efficient in vivo reactivation. Whether LAT increases reactivation by a direct effect on the reactivation process or whether it does so by increasing the establishment of latency, thereby making more latently infected neurons available for reactivation, is unclear. In mice, LAT-negative mutants appear to establish latency in fewer neurons than does wild-type HSV-1. However, this has not been confirmed in the rabbit, and the role of LAT in the establishment of latency remains controversial. To pursue this question, we inserted the gene for the enhanced green fluorescent protein (EGFP) under control of the LAT promoter in a LAT-negative virus (DeltaLAT-EGFP) and in a LAT-positive virus (LAT-EGFP). Sixty days after ocular infection, trigeminal ganglia (TG) were removed from the latently infected rabbits, sectioned, and examined by fluorescence microscopy. EGFP was detected in significantly more LAT-EGFP-infected neurons than DeltaLAT-EGFP-infected neurons (4.9% versus 2%, P < 0.0001). The percentages of EGFP-positive neurons per TG ranged from 0 to 4.6 for DeltaLAT-EGFP and from 2.5 to 11.1 for LAT-EGFP (P = 0.003). Thus, LAT appeared to increase neuronal latency in rabbit TG by an average of two- to threefold. These results suggest that LAT enhances the establishment of latency in rabbits and that this may be one of the mechanisms by which LAT enhances spontaneous reactivation. These results do not rule out additional LAT functions that may be involved in maintenance of latency and/or reactivation from latency.

Corneal macrophage infiltrates following ocular herpes simplex virus type 1 challenge vary in BALB/c mice vaccinated with different vaccines.

Macrophage cell infiltrates in the cornea were examined following ocular herpes simplex virus type 1 (HSV-1) challenge of vaccinated BALB/c mice. Mice were vaccinated with individual HSV-1 glycoproteins, cocktails of different HSV-1 glycoproteins, or live avirulent HSV-1 (strain KOS). Cryostat sections of cornea were taken at different times after challenge and reacted with M1/70, F4/80, BM8, or MOMA-1 monoclonal antibodies. The pattern of macrophage responses in the cornea differed depending on the vaccine that was given prior to HSV-1 ocular challenge. No macrophage response was detected in mice vaccinated with the highly protective 5gPs consisting of the five glycoproteins gB, gC, gD, gE, and gI. In contrast, mock vaccinated mice and mice vaccinated with gK, which is known to exacerbate HSV-1 induced eye disease, had high sustained macrophage responses. Mice vaccinated with 7gPs (5gPs+gG and gH) had moderate levels of macrophages. It appeared that (1) the most effective vaccines induced no detectable infiltrating macrophages in the eyes, while the least efficacious vaccines had very high levels of infiltrating macrophages; (2) presence of CD11b(+) cells in the cornea appeared to correlate with enhanced blepharitis, but did not appear to affect corneal scarring; and (3) presence of F4/80(+) cells in the cornea tended to correlate with increased corneal scarring.

Perforin pathway is essential for protection of mice against lethal ocular HSV-1 challenge but not corneal scarring.

Perforin (cytolysin; pore-forming protein) is expressed in both CD8(+) cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and is a major factor responsible for the cytolytic activities of these cells. Both CD8(+) T-cells and NK cells are important in eliminating cells infected with certain viruses. We examined the role of perforin in a mouse model of HSV-1 infection using perforin-deficient mice. Naïve perforin knockout (perforin(0/0)) mice were more susceptible to lethal HSV-1 ocular challenge (60% survival), than naïve parental C57BL/6 (100% survival). In contrast, both C57BL/6 and perforin(0/0) mice had similar levels of HSV-1 induced corneal scarring. Vaccination of perforin(0/0) mice induced a significantly higher HSV-1 neutralizing antibody titer than vaccination of C57BL/6 mice, and the mice were completely protected against lethal ocular challenge. These results suggest that in naïve mice ocularly challenged with HSV-1, the perforin pathway was involved in protection against death, but not in protection against corneal scarring.

Either a CD4(+)or CD8(+)T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice.

Following ocular infection of normal mice, herpes simplex virus type 1 (HSV-1) establishes a latent infection in the trigeminal ganglia (TG) with the complete absence of detectable infectious virus. In this study, the role of CD4(+)and CD8(+)T cell dependent immune responses is examined in relation to clearing infectious virus from the TG following HSV-1 ocular challenge. Nude mice, which lack T cells, and MHC(o/o)mice, which lack both MHC class I and MHC class II, were challenged ocularly with wild-type HSV-1. Over 70% of the TG from mice surviving the infection contained infectious virus, indicative of a chronic infection in these TG, rather than a latent infection. No infectious virus was detected in TGs from infected C57BL/6 parental mice. Ocular challenge of CD4(o/o)A(beta(o/o, CD8(o/o)or beta(2)m(o/o)mice resulted in latent rather than chronic infection. Similarly, when C57BL/6 mice were depleted for CD4(+)or CD8(+)T cells from 4 days before ocular challenge to 26 days after ocular challenge, no free virus was detected in TGs of challenged mice. In contrast, when mice were depleted of both their CD4(+)and CD8(+)T cells, over 90% of TGs were positive for free virus, suggesting that the lack of virus clearance was due to the combined lack of both CD4(+)T cells and CD8(+)T cells (i.e. in the presence of either CD4(+)T cells or CD8(+)T cells alone all of the infectious virus was cleared and latency was established).))