No evidence of aberrant amyloid β and phosphorylated tau expression in herpes simplex virus‐infected neurons of the trigeminal ganglia and brain

Background: Amyloid-β (Aβ), the key constituent of Alzheimer’s disease (AD) plaques, has antimicrobial properties. Objective: To investigate the association between plasma Aβ and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae. Methods: Plasma from 339 AD cases, obtained on average 9.4 years (±4.00) before diagnosis, and their matched controls were analyzed for Aβ40 and Aβ42 concentrations with Luminex xMAP technology and INNOBIA plasma Aβ-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 163 of the cases. Results: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of Aβ42 or Aβ40 in cases or controls. Conclusion: Levels of plasma Aβ were not associated with antibodies against different AD-related Spathogens.

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Herpes simplex virus type 2 transcripts in trigeminal ganglia during acute and latent infection in mice

Journal of the Neurological Sciences ◽

10.1016/0022-510x(89)90194-9 ◽

1989 ◽

Vol 93 (2-3) ◽

pp. 239-251 ◽

Cited By ~ 7

Author(s):

Satoshi Suzuki ◽

John R. Martin

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Latent Infection ◽

Trigeminal Ganglia ◽

Simplex Virus

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Herpes Simplex Virus Type 1 Corneal Infection Results in Periocular Disease by Zosteriform Spread

Journal of Virology ◽

10.1128/jvi.75.11.5069-5075.2001 ◽

2001 ◽

Vol 75 (11) ◽

pp. 5069-5075 ◽

Cited By ~ 47

Author(s):

Bretton C. Summers ◽

Todd P. Margolis ◽

David A. Leib

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Skin Lesions ◽

Ocular Infection ◽

Trigeminal Ganglia ◽

Corneal Infection ◽

Recombinant Viruses ◽

Viral Spread ◽

Reporter Activity ◽

Simplex Virus

ABSTRACT In humans and animal models of herpes simplex virus infection, zosteriform skin lesions have been described which result from anterograde spread of the virus following invasion of the nervous system. Such routes of viral spread have not been fully examined following corneal infection, and the possible pathologic consequences of such spread are unknown. To investigate this, recombinant viruses expressing reporter genes were generated to quantify and correlate gene expression with replication in eyes, trigeminal ganglia, and periocular tissue. Reporter activity peaked in eyes 24 h postinfection and rapidly fell to background levels by 48 h despite the continued presence of viral titers. Reporter activity rose in the trigeminal ganglia at 60 h and peaked at 72 h, concomitant with the appearance and persistence of infectious virus. Virus was present in the periocular skin from 24 h despite the lack of significant reporter activity until 84 h postinfection. This detection of reporter activity was followed by the onset of periocular disease on day 4. Corneal infection with a thymidine kinase-deleted reporter virus displayed a similar profile of reporter activity and viral titer in the eyes, but little or no detectable activity was observed in trigeminal ganglia or periocular tissue. In addition, no periocular disease symptoms were observed. These findings demonstrate that viral infection of periocular tissue and subsequent disease development occurs by zosteriform spread from the cornea to the periocular tissue via the trigeminal ganglion rather than by direct spread from cornea to the periocular skin. Furthermore, clinical evidence is discussed suggesting that a similar mode of spreading and disease occurs in humans following primary ocular infection.

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Effects of topical applications of phosphonoacetate on colonization of mouse trigeminal ganglia with herpes simplex virus type 1.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.26.1.65 ◽

1984 ◽

Vol 26 (1) ◽

pp. 65-68 ◽

Cited By ~ 3

Author(s):

R J Klein ◽

A E Friedman-Kien ◽

L Kaley ◽

E Brady

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Trigeminal Ganglia ◽

Simplex Virus ◽

Topical Applications

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Potential Role for Luman, the Cellular Homologue of Herpes Simplex Virus VP16 (α Gene trans-Inducing Factor), in Herpesvirus Latency

Journal of Virology ◽

10.1128/jvi.74.2.934-943.2000 ◽

2000 ◽

Vol 74 (2) ◽

pp. 934-943 ◽

Cited By ~ 57

Author(s):

Rui Lu ◽

Vikram Misra

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Viral Replication ◽

Productive Infection ◽

Trigeminal Ganglia ◽

Mutant Form ◽

Gene Promoters ◽

Intracellular Location ◽

Simplex Virus ◽

Hsv 1

ABSTRACT The cascade of herpes simplex virus (HSV) gene expression that results in viral replication begins with the activation of viral immediate-early (IE) genes by the virion-associated protein VP16. VP16 on its own is inefficient at associating with complexes formed on IE gene promoters and depends upon the cellular factor HCF for its activity. In this respect VP16 mimics the host basic leucine zipper (bZIP) protein Luman, which also requires HCF for activating transcription. Our objective is to explore interactions between Luman and HCF and to determine if they play a role in the biology of herpesviruses. In this report we show that in cultured cells ectopically expressed Luman was retained in the cytoplasm, where it colocalized with Calnexin, a protein normally associated with the endoplasmic reticulum (ER). Retention of Luman in the ER depends on a hydrophobic segment of the protein that probably serves as a transmembrane domain. Deletion of this domain changed the intracellular location of Luman so that most of the mutant protein was in the nucleus of cells. While HCF was present in the nucleus of most cells, in cells expressing Luman it was retained in the cytoplasm where the two proteins colocalized. This cytoplasmic association of Luman and HCF could also be demonstrated in neurons in trigeminal ganglia removed from cattle soon after death. Cells in tissue culture that expressed Luman, but not a mutant form of the protein that fails to bind HCF, were resistant to a productive infection with HSV type 1 (HSV-1). We hypothesize that similar Luman-HCF interactions in sensory neurons in trigeminal ganglia result in the suppression of viral replication and the establishment of latency. Interestingly, Luman could activate the promoters of IE110 and LAT, two genes that are critical for reactivation of HSV-1 from latency. This suggests a role for Luman in the reactivation process as well.

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