We performed immunoperoxidase stains on skin biopsies taken from nine patients with recurrent peripheral herpes simplex lesions at 12 h to 6 d after onset of signs of symptoms to phenotype the inflammatory infiltrate, to detect cells producing interferons alpha and gamma, and to locate herpes simplex virus antigen-containing cells. Viral glycoprotein antigen was located in the nuclei and cytoplasm of necrotic epidermal cells, often within vesicles, in biopsies taken between the first and third day. Histologically, biopsies of all stages showed intradermal focal perivascular and diffuse mononuclear inflammatory infiltrates. The cells constituting the infiltrates were predominantly T lymphocytes with lesser numbers of histiocytes; Leu 7+ (most natural killer/killer) cells and B cells were rare in the biopsy specimens. Leu 3a+ ("helper") T lymphocytes predominated in both subepidermal and perivascular regions of early lesions (12-24 h). Tissue helper/suppressor ratios ranged from 6.3 to 3.4 compared with 1.9-1.0 in blood. In later lesions (after 2 d), monocytes/macrophages were more prominent in tissue sections and the helper/suppressor ratios (2.3-2.5) more nearly approximated those of blood (1.6-2.7). The negative correlation of tissue ratios with time was significant (P less than or equal to 0.02). A large proportion of the infiltrated T lymphocytes expressed DR antigens. There was also diffuse strong DR expression on epidermal cells in five cases (all of two or more days). In six biopsies, scattered macrophages and small cells, presumably lymphocytes, demonstrated cytoplasmic or membrane staining for a substance which copurifies with interferon gamma. We identified such stained cells within vessels, suggesting that these cells circulate. Gamma interferon might have an important role within the herpetic lesions, possibly inducing macrophage activation and cytotoxic T lymphocytes and increasing DR expression on monocyte and epidermal cells.
A L Cunningham, R R Turner, A C Miller, M F Para, T C Merigan
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Herpes simplex virus assembly and spread in murine skin after infection from the outside
Richardo T, Liu X, Döhner K, Chao TY, Buch A, Binz A, Pohlmann A, de le Roi M, Baumgärtner W, Brand K, Bauerfeind R, Förster R, Sodeik B, Halle S |
Journal of Virology | 2025 |
Herpes simplex virus type-1 infection and spread in a novel porcine corneal explant model is restricted to the epithelium
Arshad S, Rana H, Truong NR, Pattamatta U, Bertram KM, White A, Chinnery HR, Carnt NA, Cunningham AL |
PLOS Pathogens | 2025 |
Herpes simplex virus spreads rapidly in human foreskin, partly driven by chemokine-induced redistribution of Nectin-1 on keratinocytes
Rana H, Truong NR, Johnson B, Baharlou H, Herbert JJ, Kandasamy S, Goddard R, Cohen RC, Wines M, Nasr N, Harman AN, Bertram KM, Sandgren KJ, Cunningham AL |
PLoS pathogens | 2024 |
An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application.
Su D, Han L, Shi C, Li Y, Qian S, Feng Z, Yu L |
Virulence | 2024 |
Breaching the Barrier: Investigating Initial Herpes Simplex Viral Infection and Spread in Human Skin and Mucosa
Rana H, Truong NR, Sirimanne DR, Cunningham AL |
Viruses | 2024 |
The Dilemma of HSV-1 Oncolytic Virus Delivery: The Method Choice and Hurdles
Tang G, Wang D, Zhao X, Feng Z, Chen Q, Shen Y |
International journal of molecular sciences | 2023 |
Interferon inhibits the release of herpes simplex virus-1 from the axons of sensory neurons
Danastas K, Guo G, Merjane J, Hong N, Larsen A, Miranda-Saksena M, Cunningham AL |
mBio | 2023 |
Immunogenicity in Mice Immunized with Recombinant Adenoviruses Expressing Varicella-Zoster Virus Envelope Glycoprotein E.
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HSV-2-Specific Human Female Reproductive Tract Tissue Resident Memory T Cells Recognize Diverse HSV Antigens
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Frontiers in immunology | 2022 |
Cytokines and chemokines: The vital role they play in herpes simplex virus mucosal immunology
Smith JB, Herbert JJ, Truong NR, Cunningham AL |
Frontiers in immunology | 2022 |
B cells, antibody-secreting cells and virus-specific antibodies respond to herpes simplex virus-2 reactivation in skin
Emily S. Ford, Anton M. Sholukh, RuthMabel Boytz, Savanna Carmack, Alexis Klock, Khamsone Phasouk, Jason Shao, Raabya Rossenkhan, Paul T. Edlefsen, Tao Peng, Christine Johnston, Anna Wald, Jia Zhu, Lawrence Corey |
Journal of Clinical Investigation | 2021 |
The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection
TR ONeil, K Hu, NR Truong, S Arshad, BL Shacklett, AL Cunningham, N Nasr |
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S Zhu, A Viejo-Borbolla |
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PLoS pathogens | 2021 |
Vaccines against Genital Herpes: Where Are We?
HC Kim, HK Lee |
Human vaccines | 2020 |
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RJ Diefenbach, C Fraefel |
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Herpes Simplex Virus: Methods and Protocols
RJ Diefenbach, C Fraefel |
2019 | |
Mechanisms of Immune Control of Mucosal HSV Infection: A Guide to Rational Vaccine Design
NR Truong, JB Smith, KJ Sandgren, AL Cunningham |
Frontiers in immunology | 2019 |
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H McTavish, KW Zerebiec, JC Zeller, LL Shekels, MA Matson, BT Kren |
Immunity, Inflammation and Disease | 2019 |
Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older
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The Journal of Infectious Diseases | 2018 |
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JR Cabrera, AJ Charron, DA Leib, RM Longnecker |
Journal of virology | 2018 |
Tzanck yaymasının üç günden daha eski Herpes lezyonlarının tanısındaki rolü
BF Karaman |
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RA Botting, H Rana, KM Bertram, JW Rhodes, H Baharlou, N Nasr, AL Cunningham, AN Harman |
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Journal of virology | 2017 |
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JT Schiffer, SL Gottlieb |
Vaccine | 2017 |
Reference Module in Materials Science and Materials Engineering
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Reference Module in Materials Science and Materials Engineering | 2017 |
Dendritic cells in the cornea during Herpes simplex viral infection and inflammation
MS Kwon, NA Carnt, NR Truong, U Pattamatta, AJ White, C Samarawickrama, AL Cunningham |
Survey of Ophthalmology | 2017 |
Understanding natural herpes simplex virus immunity to inform next-generation vaccine design
KJ Sandgren, K Bertram, AL Cunningham |
IBMS BoneKEy | 2016 |
Chitosan as an Immunomodulating Adjuvant on T-Cells and Antigen-Presenting Cells in Herpes Simplex Virus Type 1 Infection
B Choi, DH Jo, AK Anower, SM Islam, S Sohn |
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K Kabashima |
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IE Flesch, KL Randall, NA Hollett, HD Law, LA Miosge, Y Sontani, CC Goodnow, DC Tscharke |
Immunology and Cell Biology | 2015 |
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M Ghebremichael |
Journal of Applied Statistics | 2015 |
Herpes Simplex Virus Type 2–Infected Dendritic Cells Produce TNF-α, Which Enhances CCR5 Expression and Stimulates HIV Production from Adjacent Infected Cells
V Marsden, H Donaghy, KM Bertram, AN Harman, N Nasr, E Keoshkerian, S Merten, AR Lloyd, AL Cunningham |
Journal of immunology (Baltimore, Md. : 1950) | 2015 |
Manual of Clinical Microbiology
JH Jorgensen, KC Carroll, G Funke, MA Pfaller, ML Landry, SS Richter, DW Warnock |
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S Awasthi, HM Friedman |
Current Opinion in Virology | 2014 |
Plasma and Cerebrospinal Fluid Herpes Simplex Virus Levels at Diagnosis and Outcome of Neonatal Infection
AJ Melvin, KM Mohan, JT Schiffer, LM Drolette, A Magaret, L Corey, A Wald |
The Journal of Pediatrics | 2014 |
DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity
Q Zhang, CG Dove, JL Hor, HM Murdock, DM Strauss-Albee, JA Garcia, JN Mandl, RA Grodick, H Jing, DB Chandler-Brown, TE Lenardo, G Crawford, HF Matthews, AF Freeman, RJ Cornall, RN Germain, SN Mueller, HC Su |
Journal of Experimental Medicine | 2014 |
Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis
CM Hull, MJ Levin, SK Tyring, SL Spruance |
Antimicrobial agents and chemotherapy | 2014 |
HIV, hepatitis viruses and viral STIs: intertwined fates?
T Cunningham |
Microbiology Australia | 2014 |
The herpes simplex virus 1-encoded envelope glycoprotein B activates NF-κB through the Toll-like receptor 2 and MyD88/TRAF6-dependent signaling pathway
M Cai, M Li, K Wang, S Wang, Q Lu, J Yan, KL Mossman, R Lin, C Zheng |
PloS one | 2013 |
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JT Schiffer, L Corey |
Nature Medicine | 2013 |
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Y Ogawa, T Kawamura, T Matsuzawa, R Aoki, P Gee, A Yamashita, K Moriishi, K Yamasaki, Y Koyanagi, A Blauvelt, S Shimada |
Cell Host & Microbe | 2013 |
The Immunologic Basis for Severe Neonatal Herpes Disease and Potential Strategies for Therapeutic Intervention
S Gantt, WJ Muller |
Clinical and Developmental Immunology | 2013 |
Immune Surveillance by CD8αα+ Skin Resident T Cells in Human Herpesvirus Infection
J Zhu, T Peng, C Johnston, K Phasouk, AS Kask, A Klock, L Jin, K Diem, DM Koelle, A Wald, H Robins, L Corey |
Nature | 2013 |
Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract
JT Schiffer, D Swan, RA Sallaq, A Magaret, C Johnston, KE Mark, S Selke, N Ocbamichael, S Kuntz, J Zhu, B Robinson, ML Huang, KR Jerome, A Wald, L Corey |
eLife | 2013 |
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CM Hull, MJ Levin, SK Tyring, SL Spruance |
Antimicrobial agents and chemotherapy | 2013 |
The Role of Sexually Transmitted Infections in HIV-1 Progression: A Comprehensive Review of the Literature
HM Chun, RJ Carpenter, GE Macalino, NF Crum-Cianflone |
Journal of Sexually Transmitted Diseases | 2013 |
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Journal of Clinical Investigation | 2012 |
Herpes simplex virus antigens directly activate NK cells via TLR2, thus facilitating their presentation to CD4 T lymphocytes
M Kim, NR Osborne, W Zeng, H Donaghy, K McKinnon, DC Jackson, AL Cunningham |
Journal of immunology (Baltimore, Md. : 1950) | 2012 |
Immunology in the Clinic Review Series; focus on host responses: T cell responses to herpes simplex viruses
KJ Laing, L Dong, J Sidney, A Sette, DM Koelle |
Clinical & Experimental Immunology | 2012 |
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LK Dropulic, JI Cohen |
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Deciphering the epidemic synergy of herpes simplex virus type 2 (HSV-2) on human immunodeficiency virus type 1 (HIV-1) infection among women in sub-Saharan Africa
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Theoretical Biology and Medical Modelling | 2011 |
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GE Gross, SK Tyring |
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Immunology and Cell Biology | 2010 |
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The Journal of Infectious Diseases | 2008 |
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Immunodominant Epitopes in Herpes Simplex Virus Type 2 Glycoprotein D Are Recognized by CD4 Lymphocytes from Both HSV-1 and HSV-2 Seropositive Subjects1
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Cellular Microbiology | 2006 |
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BT Rouse, SD Kaistha |
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The Journal of Infectious Diseases | 2006 |
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American Journal of Reproductive Immunology | 2005 |
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The Journal of Infectious Diseases | 2005 |
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Blood | 2005 |
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Viral Immunology | 2005 |
Developments in STD/HIV Interactions: The Intertwining Epidemics of HIV and HSV-2
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Infectious Disease Clinics of North America | 2005 |
Regulated Expression of Galectin-1 after In Vitro Productive Infection with Herpes Simplex Virus Type I: Implications for T Cell Apoptosis
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International journal of immunopathology and pharmacology | 2005 |
Herpes Simplex Virus Infection of Human Dendritic Cells Induces Apoptosis and Allows Cross-Presentation via Uninfected Dendritic Cells
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Journal of immunology (Baltimore, Md. : 1950) | 2005 |
Protective Immunity to Genital Herpes Simpex Virus Type 2 Infection Is Mediated by T-bet
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Journal of immunology (Baltimore, Md. : 1950) | 2005 |
Clearance of Herpes Simplex Virus Type 2 by CD8 + T Cells Requires Gamma Interferon and either Perforin- or Fas-Mediated Cytolytic Mechanisms
ME Dobbs, JE Strasser, CF Chu, C Chalk, GN Milligan |
Journal of virology | 2005 |
CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals
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Journal of General Virology | 2004 |
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The Journal of Infectious Diseases | 2004 |
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Journal of Medical Virology | 2004 |
The Effects of Herpes Simplex Virus-2 on HIV-1 Acquisition and Transmission: A Review of Two Overlapping Epidemics
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JAIDS Journal of Acquired Immune Deficiency Syndromes | 2004 |
Genital ulcer disease control and HIV prevention
R Steen, G Dallabetta |
Journal of Clinical Virology | 2004 |
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E Guigné, J Revuz, JC Roujeau |
Skin Immune System: Cutaneous Immunology and Clinical Immunodermatology, Third Edition | 2004 |
Calculating the Contribution of Herpes Simplex Virus Type 2 Epidemics to Increasing HIV Incidence: Treatment Implications
S Blower, L Ma |
Clinical Infectious Diseases | 2004 |
Absence of Intercellular Adhesion Molecule 1 Expression in Varicella Zoster Virus–infected Keratinocytes During Herpes Zoster: Another Immune Evasion Strategy?
AF Nikkels, C Sadzot-Delvaux, GE Piérard |
The American Journal of Dermatopathology | 2004 |
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DM Koelle, L Corey |
Clinical microbiology reviews | 2003 |
The role of dendritic cells in immune responses against vaginal infection by herpes simplex virus type 2
A Iwasaki |
Microbes and Infection | 2003 |
HSV-1 antigens and DNA in the corneal explant buttons of patients with non-herpetic or clinically atypical herpetic stromal keratitis
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The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B
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Expression of Cutaneous Lymphocyte-Associated Antigen and Functional E-Selectin Ligand by CD8+ T-cells Specific for a Skin-Tropic Virus
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Journal of Clinical Investigation | 2002 |
Home sweet home: How do virus-specific T cells navigate to the skin?
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Journal of Clinical Investigation | 2002 |
El chancroide
PZ Diego, MA Martín, BS Colomo |
Piel | 2002 |
Vaccines Against Genital Herpes: Progress and Limitations
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Drugs | 2002 |
Herpesviruses and Immunity
PG Medveczky, H Friedman, M Bendinelli |
2002 | |
Viral Proteins Counteracting Host Defenses
UH Koszinowski, H Hengel |
2002 | |
A candidate phocid herpesvirus vaccine that provides protection against feline herpesvirus infection
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Vaccine | 2001 |
Herpes simplex virus-specific immune responses in subjects with frequent and infrequent orofacial recrudescences
DB Mckenna, WA Neill, M Norval |
British Journal of Dermatology | 2001 |
Infection of murine keratinocytes with herpes simplex virus type 1 induces the expression of interleukin-10, but not interleukin-1 alpha or tumour necrosis factor-alpha
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Immunology | 2001 |
Alpha and gamma interferons inhibit herpes simplex virus type 1 infection and spread in epidermal cells after axonal transmission
Z Mikloska, AL Cunningham |
Journal of virology | 2001 |
Immature monocyte-derived dendritic cells are productively infected with herpes simplex virus type 1
Z Mikloska, L Bosnjak, AL Cunningham |
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CD8 CTL from Genital Herpes Simplex Lesions: Recognition of Viral Tegument and Immediate Early Proteins and Lysis of Infected Cutaneous Cells
DM Koelle, HB Chen, MA Gavin, A Wald, WW Kwok, L Corey |
Journal of immunology (Baltimore, Md. : 1950) | 2001 |
Chancroid: From Clinical Practice to Basic Science
DA Lewis |
AIDS Patient Care and STDs | 2000 |
Reactivation of Human Herpesviruses after Allogeneic Peripheral Blood Stem Cell Transplantation and Bone Marrow Transplantation
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An overview of sexually transmitted diseases. Part III. Sexually transmitted diseases in HIV-infected patients
A Czelusta, A Yen-Moore, MV der Straten, D Carrasco, SK Tyring |
Journal of the American Academy of Dermatology | 2000 |
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Immune Protection against HSV-2 in B-Cell-Deficient Mice
KL Dudley, N Bourne, GN Milligan |
Virology | 2000 |
Why do we lack an effective vaccine against herpes simplex virus infections?
SP Deshpande, U Kumaraguru, BT Rouse |
Microbes and Infection | 2000 |
Monophosphoryl Lipid A and QS21 Increase CD8 T Lymphocyte Cytotoxicity to Herpes Simplex Virus-2 Infected Cell Proteins 4 and 27 Through IFN-γ and IL-12 Production
Z Mikloska, M Rückholdt, I Ghadiminejad, H Dunckley, M Denis, AL Cunningham |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease
PA Fox, SE Barton, N Francis, M Youle, DC Henderson, D Pillay, MA Johnson, L Fearfield, BG Gazzard, CB Bunker |
HIV Medicine | 1999 |
Recurrent Herpes Simplex Infection from Western and Traditional Chinese Medicine Viewpoints
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Acupuncture in Medicine | 1999 |
Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of HSV-specific cytotoxic T lymphocytes
DM Koelle, CM Posavad, GR Barnum, ML Johnson, JM Frank, L Corey |
Journal of Clinical Investigation | 1998 |
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M Schomogyi, A Wald, L Corey |
Infectious Disease Clinics of North America | 1998 |
Differential effect of phototherapy on the activities of human natural killer cells and cytotoxic T cells
WA Neill, KE Halliday, M Norval |
Journal of Photochemistry and Photobiology B: Biology | 1998 |
Tipping the scales of herpes simplex virus reactivation: the important responses are local
C M Posavad, D M Koelle, L Corey |
Nature Medicine | 1998 |
Molecular Aspects of Herpes Simplex Virus I Latency, Reactivation, and Recurrence
CS Miller, RJ Danaher, RJ Jacob |
Critical Reviews in Oral Biology & Medicine | 1998 |
Herpes simplex virus seropositivity and reactivation at delivery among pregnant women infected with human immunodeficiency virus-1
J Hitti, DH Watts, SK Burchett, T Schacker, S Selke, ZA Brown, L Corey |
American Journal of Obstetrics and Gynecology | 1997 |
Preferential presentation of herpes simplex virus T-cell antigen by HLA DQA1*0501/DQB1*0201 in comparison to HLA DQA1*0201/DQB1*0201
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Human Immunology | 1997 |
Growth of herpes simplex type 1 on skin explants of atopic eczema
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Clinical and Experimental Dermatology | 1996 |
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JJ Oord, R Vos, C Wolf-Peeters |
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AM Arvin |
Infectious Disease Clinics of North America | 1996 |
Small, freshly arrived histiocytes in cutaneous and mucosal herpetic lesions
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Cytotoxic T-Lymphocytes in Human Viral and Malaria Infections
MB Oldstone |
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Herpes simplex virus type 2 infection of heterosexual men attending a sexual health centre
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The Medical Journal of Australia | 1994 |
Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8+ cytotoxic T lymphocytes
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Herpes simplex virus infections during the decade since the licensure of acyclovir
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Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture
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Baillière's Clinical Obstetrics and Gynaecology | 1993 |
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Herpes simplex keratitis: Role of viral infection versus immune response
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Role of keratinocytes in human recurrent herpetic lesions. Ability to present herpes simplex virus antigen and act as targets for T lymphocyte cytotoxicity in vitro
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Inhibitory Effect of Gamma Interferon on Cultured Human Keratinocyte Thrombospondin Production, Distribution, and Biologic Activities
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Is Recombinant Interleukin-2 the Best Way to Deliver Interferon-γ in Human Disease?
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The histopathologic identification of CMV infected cells in biopsies of human renal allografts
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New England Journal of Medicine | 1986 |
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