Regulation of glycoprotein D synthesis of herpes simplex virus 1 by α 4 protein,the major regulatory protein of the virus,in stably transformed cell lines: effect of the relative gene copy numbers

Summary Earlier studies concerning 1 gene regulation by the 4 protein, the major regulatory protein of herpes simplex virus 1 (HSV-1), in stably transformed cell lines, reported conflicting results, i.e., 4 protein positively regulated the ₁ gB gene in 4/gB cells, while it negatively regulated the ₁ gD gene in 4/BJ cells. Both cell lines were derived from a common parental cell line 4/c 113 that contains 1 copy of the 4 gene, and the only apparent difference between them was the relative copy number of the gB and gD sequences (1 and 30–50, respectively) resident in the cell genome. We investigated this disparity by constructing a cell line (BA 4) that contains one copy each of the 4 and ₁ gD sequences, by fusion of 4/c 113 and BJt cells, containing and expressing respectively 1 copy of the 4 and gD genes. BA 4 cells constitutively expressed both the 4, gD genes inherited from the parental cell lines ( 4/c 113 and BJt). In BA 4 cells the 4 protein positively regulates the gD gene as evidenced from (i) higher levels of gD expression than the parental BJt cells lacking the 4 gene, and (ii) significant decrease in gD expression under conditions that render the 4 protein produced in BA 4 cells non-functional. In addition the ₂gG gene contained within the DNA fragment encoding the gD gene, is also expressed in BA 4 cells. On the basis of these data, we propose that gene regulation by the 4 protein is affected by the relative copy number of these genes, resident in the cell genome.     

Effect of Gardenia extract ZG on the adsorption quantity of herpes simplex virus type 1 （HSV-1）

To observe the effect of Gardenia extract ZG on the adsorption quantity of herpes simplex virus type 1 (HSV-1) so as to explore the mechanism of its antiviral activity, fluorescein isothiocyanate (FITC) was used as the fluorescent probe to label viruses and heparin sodium was used as control. Meanwhile , the effect of Gardenia extract ZG on the adsorption quantity on the surface of Hep-2 cells was determined by flow cytometry. It was demonstrated that adsorption of HSV-1 on the surface of Hep-2 cells exhibited the character of saturation and specificity and heparin sodium could prevent attachment of viruses on these cells. These results are in accord with those reported previously. It was also proved that the manner of drug-use prior to adsorption or simultaneous use of drug and adsorption was better than adsorption prior to drug-use, and the inhibition rates of the former and latter manner were 84. 76% and 82.92% respectively. Three manners of drug-use with Gardenia extract ZG were all effective to reduce the adsorption quantity of viruses, especially the manner of simultaneous use of drug and adsorption with an adsorption inhibition rate of 68.46% . From the above observation, it is apparent that the mechanism of anti-viral activity of Gardenia extract ZG may be via several steps involved in the HSV-1 adsorption.     

Simian TRIM5α proteins reduce replication of herpes simplex virus

Old World monkey TRIM5α proteins are known to block the replication of human immunodeficiency virus and other retroviruses in a species-specific fashion. In this report, we show that specific forms of simian TRIM5α proteins can restrict herpes simplex virus (HSV) infection. To define the effect of TRIM5α on HSV replication, we examined HSV infection in HeLa cell lines that stably express simian and human orthologs of TRIM5α proteins. We demonstrated that several simian TRIM5α proteins can restrict HSV replication, with the TRIM5α protein of rhesus macaques showing the strongest inhibition of HSV infection. We also found that the level of the inhibition of virus replication was viral strain-specific. TRIM5α is likely to inhibit HSV at the early stage of infection; however, at later times of infection, the levels of TRIM5α are significantly decreased. Thus, some TRIM5α proteins exhibit antiviral effects that extend beyond retroviral infections, but HSV may be able to reduce this restriction by reducing TRIM5α levels during the later phases of virus replication. Our results also argue that TRIM5α is only part of the reduced level of HSV replication in rhesus macaques, which are known to be less susceptible to HSV infection than other primates.     

Epidemiology of herpes simplex virus types 1 and 2 in Germany: what has changed?

Infections with herpes simplex virus (HSV) types 1 and 2 are widespread in all human populations and result in persistent and latent infections. HSV-1 is commonly responsible for orofacial, HSV-2 more likely causes genital lesions. Herpes genitalis is one of the most important sexually transmitted diseases; furthermore, there are severe diseases associated with HSV (e.g., encephalitis). Over the last years an increase in clinical manifestations of HSV has been reported, and HSV-1 has been increasingly discussed as causative agent of herpes genitalis. We retrospectively evaluated the laboratory results of our routine diagnostic service for HSV infections, looking for changes of HSV epidemiology in recent years. Specimens from 2,678 herpes patients were obtained between 1 January 1996 and 31 March 2002. Using cell culture, the presence of HSV was investigated in swabs taken from different body sites, and clinical data on HSV localization and type were evaluated. We found 345 patients positive for HSV-1 and 212 positive for HSV-2. Clinical data were available from 72.1% of the patients with HSV-1, and 61.3% of those with HSV-2 infection. In genital herpes HSV-1 was the causative agent in 20% of men and in 25% of women. In patients suffering from orofacial herpes HSV-2 was detected in 7% of men and in 4% of women. To evaluate the frequency of neurological HSV diseases, 2,406 cerebrospinal fluid samples (CSF) from 2,121 patients suspected of meningitis or encephalitis were tested for HSV DNA by the polymerase chain reaction. Among those patients, 120 showed CSF positive for HSV DNA. Serum surveys of HSV-1 and HSV-2 infection recently established in our region were compared to similar studies performed in Germany 25 years ago. We found that seroprevalences have not changed over the last 25 years and that neurological HSV diseases are rare. However, as in the USA, a significant percentage of herpes genitalis is caused by HSV-1 in Germany.     

Dysregulation of cofilin-1 activity—the missing link between herpes simplex virus type-1 infection and Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a multifactorial disease triggered by environmental factors in combination with genetic predisposition. Infectious agents, in particular herpes simplex virus type 1 (HSV-1), are gradually being recognised as important factors affecting the development of AD. However, the mechanism linking HSV-1 and AD remains unknown. Of note, HSV-1 manipulates the activity of cofilin-1 to ensure their efficient infection in neuron cells. Cofilin-1, the main regulator of actin cytoskeleton reorganization, is implicating for the plastic of dendritic spines and axon regeneration of neuronal cells. Moreover, dysfunction of cofilin-1 is observed in most AD patients, as well as in mice with AD and ageing. Further, inhibition of cofilin-1 activity ameliorates the host cognitive impairment in an animal model of AD. Together, dysregulation of cofilin-1 led by HSV-1 infection is a potential link between HSV-1 and AD. Herein, we critically summarize the role of cofilin-1-mediated actin dynamics in both HSV-1 infection and AD, respectively. We also propose several hypotheses regarding the connecting roles of cofilin-1 dysregulation in HSV-1 infection and AD. Our review provides a foundation for future studies targeting individuals carrying HSV-1 in combination with cofilin-1 to promote a more individualised approach for treatment and prevention of AD.     

Consequences of CXCL10 and IL-6 induction by the murine IFN-α1 transgene in ocular herpes simplex virus type 1 infection

Herpes simplex virus type 1 infection of the mouse eye results in an impressive inflammatory response culminating in the death of the animal or the establishment of a “latent” infection depending on a number of ill-defined variables that include components of the innate and adaptive immune system. The application of type I interferon transgenes has been found to antagonize viral replication and spread from the eye to the nervous system. Associated with the in situ transfection of the cornea is the upregulation of two inflammatory molecules, interleukin-6 and CXCL10. In this article, we will further examine the contribution these molecules may have in the host response to ocular infection with herpes simplex virus type 1.     

Effect of herpes simplex virus type-1 UL41 gene on the stability of mRNA from the cellular genes: β-actin,fibronectin, glucose transporter-1, and docking protein,and on virus intraperitoneal pathogenicity to newborn mice

Infection with HSV-1 is accompanied by the shut-off of cellular gene expression. The virion-associated function is encoded by the viral gene U_L41. An HSV-1 mutant, vhs-1, which has a genomic deletion in the U_L41 gene, is incapable of inducing the shut-off of cellular gene expression. The effect of HSV-1 infection on the shut-off of the cellular genes (or mRNA degradation) was studied specifically with the cellular genes for -actin, fibronectin, glucose transporter-1, and the docking protein. The level of these specific mRNAs was measured in cells infected with several HSV-1 strains and was compared to that of vhs-1- and mock-infected cells. It was possible to demonstrate a marked reduction in the level of the specific mRNA from these cellular genes in cells infected with several HSV-1 strains but not with the vhs-1 mutant. The pathogenicity of the HSV-1 vhs-1 mutant to newborn mice was studied. It was found that the mutant is less pathogenic to newborn mice than its parental strain HSV-1 KOS.     

The capsid protein of infectious bursal disease virus contains a functional α4β1 integrin ligand motif

Infectious bursal disease virus (IBDV), a member of the dsRNA Birnaviridae family, is an important immunosuppressive avian pathogen. We have identified a strictly conserved amino acid triplet matching the consensus sequence used by fibronectin to bind the α4β1 integrin within the protruding domain of the IBDV capsid polypeptide. We show that a single point mutation on this triplet abolishes the cell-binding activity of IBDV-derived subviral particles (SVP), and abrogates the recovering of infectious IBDV by reverse genetics without affecting the overall SVP architecture. Additionally, we demonstrate that the presence of the α4β1 heterodimer is a critical determinant for the susceptibility of murine BALB/c 3T3 cells to IBDV binding and infectivity. Our data suggests that the IBDV might also use the α4β1 integrin as a specific binding receptor in avian cells.     

Enhancement by TNF-α of reactivation and replication of latent herpes simplex virus from trigeminal ganglia of mice

Summary The influence of tumor-necrosis-factor- (TNF-), granulocytemacrophage colony-stimulating factor (GM-CSF), interleukine-1 (IL-1) and IL-3 on the in vitro reactivation frequency and replication rate of trigeminal ganglia of mice latently infected with herpes simplex virus (HSV) strain KOS was studied. It could be demonstrated that TNF- and possibility GM-CSF, but not IL-1 and IL-3, enhanced the reactivation frequency and replication of HSV. Interferon / (IFN/) prevented reactivation and replication.     

Suppression of µ1 subunit of the adaptor protein complex 2 reduces dengue virus release

Virus Genes - Dengue virus (DENV) requires clathrin-mediated endocytosis for its entry into the cells where the adaptor protein complex (AP) is vital for the clathrin-coated vesicle formation. The...     

Correlation of virus replication,cytokine (TNF-α and IL-1) producing cells,neuronal necrosis and inflammation after intranasal infection of mice with herpes simplex virus strains of different virulence

Summary The number of TNF- and IL-1 producing cells was investigated during the acute replication phase of herpes simplex virus (HSV) in trigeminal ganglia after intranasal infection with strains of different virulence. The highly virulent strain WAL replicated strongly and induced many cytokine producing cells early in the ganglia. The low virulent strain HFEM replicated less, only few cytokine producing cells were detected late. The thymidine-kinase negative (TK^–) virus 1301 did not replicate but produced some lymphocytic inflammation. The higher the virulence of strains of HSV-1 or -2 was, the stronger was the extent of histopathological lesions; moreover, a dissociation in time between replication and cellular reaction (granulocytic and lymphocytic) could be observed after infection with strains HFEM and TK^– virus 1301. CD4 and CD8 positive cells could be detected mainly at the rim of necrotic areas, TNF- and IL-1 producing cells, however, were scattered throughout the ganglia.     

Anti-CD8 treatment alters interleukin-4 but not interferon-γ mRNA levels in murine sensory ganglia during herpes simplex virus infection

Summary.  Clearance of herpes simplex virus (HSV) from sensory ganglia of infected mice is dependent on CD8⁺ cells but not on the death of infected neurons. The mechanism of action of CD8⁺ cells in HSV infected ganglia is therefore unknown. The determine which cytokines might be involved in the CD8⁺ cell dependent response to ganglionic HSV infection, IL-2, IL-4, IL-6, IL-10, and IFN-γ mRNA levels were measured in infected ganglia from immunocompetent and anti-CD8 treated mice. Anti-CD8 treatment increased the abundance of mRNA encoding IL-4, and, to a lesser extent, IL-2, and IL-6. Significantly, IFN-γ mRNA was not affected. Received May 17, 1999 Accepted June 29, 1999     

Are latent,immediate-early genes of herpes simplex virus-1 essential in causing trigeminal neuralgia?

The etiology and pathogenesis of major trigeminal neuralgia remain largely unknown, but are believed to result from an irritative lesion near the semilunar ganglion. We suggest that its primary cause is a single, active DNA sequence in the persistent but non-integrated genome of latent herpes simplex virus type 1 commonly observed in a few infected A-delta nerve fibers of the cheek. Facial pain occurs as a result of herpes virus reactivation and when supplies of neurotrophins controlling normal transport functions of axolemmal ion channels become depleted.