Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause prevalent, chronic infections that have serious outcomes in some individuals. Neonatal herpes may occur when the infant traverses the cervix during maternal genital herpes. Genital herpes is a major risk factor for human immunodeficiency virus type 1 transmission. Considerable efforts have been made to design and test vaccines for HSV, focusing on genital infection with HSV-2. Several protein subunit vaccines based on HSV-2 envelope glycoproteins have reached advanced-phase clinical trials. These antigens were chosen because they are the targets of neutralizing-antibody responses and because they elicit cellular immunity. Encouraging results have been reported in studies of treatment of HSV-seronegative women with a vaccine consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant. Because most sexual HSV transmission occurs during asymptomatic shedding, it is important to evaluate the impact of vaccination on HSV-2 infection, clinically apparent genital herpes, and HSV shedding among vaccine recipients who acquire infection. There are several other attractive formats, including subunit vaccines that target cellular immune responses, live attenuated virus strains, and mutant strains that undergo incomplete lytic replication. HSV vaccines have also been evaluated for the immunotherapy of established HSV infection.
 ...
PMID:Recent progress in herpes simplex virus immunobiology and vaccine research. 1252 27

A patient presented with acute retinal necrosis of the left eye. Demonstration of herpes simplex virus (HSV) DNA in the aqueous humour confirmed the diagnosis. Negative results of HSV type-specific antibody tests based on gG antigens suggested a primary HSV infection. However, the patient had a past history of laboratory-confirmed herpes simplex encephalitis 6 years ago. Using antibody tests based on whole viral lysate antigens, he was seropositive from the onset, and immunoblot testing confirmed a lack of anti-gG reactivity. To be able to assess whether this might be related to the apparent inability of his immune system to suppress clinically symptomatic HSV infection, serial samples were tested by an HSV neutralisation test and a whole-blood flow cytometric assay to determine the frequency of HSV-specific CD4 lymphocytes. However, this did not yield evidence of obvious immunodeficiency; the patient reacted similarly to known positive controls by both assays. Although type-specific HSV serological tests based on gG are generally more specific than those based on whole viral lysate antigens, they have a somewhat lower sensitivity, as a certain percentage of HSV-infected individuals do not develop antibodies against gG, and others may suffer a secondary loss of anti-gG reactivity. Thus there is a risk of missing individual infected patients. Unless this potential problem is recognised, serious consequences might possibly result. We therefore urge virologists and clinicians to exercise great care if highly specific antibody assays based on recombinant proteins are employed.
 ...
PMID:Acute retinal necrosis six years after herpes simplex encephalitis: an elusive immune deficit suggested by insufficient test sensitivity. 1512

Topical microbicides designed to prevent acquisition of sexually transmitted infections are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observation that herpes simplex virus (HSV) and human immunodeficiency virus bind heparan sulfate provided the rationale for the development of sulfated or sulfonated polymers as topical agents. Although several of the polymers have advanced to clinical trials, the spectrum and mechanism of anti-HSV activity and the effects on soluble mediators of inflammation have not been evaluated. The present studies address these gaps. The results indicate that PRO 2000, polystyrene sulfonate, cellulose sulfate, and polymethylenehydroquinone sulfonate inhibit HSV infection 10,000-fold and are active against clinical isolates, including an acyclovir-resistant variant. The compounds formed stable complexes with glycoprotein B and inhibit viral binding, entry, and cell-to-cell spread. The effects may be long lasting due to the high affinity and stability of the sulfated compound-virus complex, as evidenced by surface plasmon resonance studies. The candidate microbicides retained their antiviral activities in the presence of cervical secretions and over a broad pH range. There was little reduction in cell viability following repeated exposure of human endocervical cells to these compounds, although a reduction in secretory leukocyte protease inhibitor levels was observed. These studies support further development and rigorous evaluation of these candidate microbicides.
 ...
PMID:Candidate topical microbicides bind herpes simplex virus glycoprotein B and prevent viral entry and cell-to-cell spread. 1515 95

Patients with immunodeficiency or treatment-related immunosuppression are at an increased risk of developing severe herpes simplex virus (HSV) infection. We present a fatal case of a generalized HSV-1 infection in a 22-year-old female afflicted by acute lymphoblastic leukemia who was treated with polychemotherapy. The terminal clinical course was characterized by abdominal pain, progressive hepatic failure, and disseminated intravascular coagulation. Autopsy revealed non-perioral herpetic skin lesions and mucosal ulceration of the esophagus and colon. Punctuated areas of yellow-tan necrosis with hyperemic rims were detected in the liver, spleen, and lung. Numerous petechiae were observed on the mucosal surface of the esophagus, jejunum, ileum, and colon. Microscopically, lesions demonstrated the cellular changes characteristic of herpetic infection. Immunohistochemistry for identification of the virus using monoclonal antibodies against HSV-1 and HSV-2 showed positive staining for HSV-1. Polymerase chain reaction and sequencing confirmed HSV-1 positivity. Emphasis must be placed on clinical awareness of a generalized HSV infection in immunocompromised patients. Absence of orofacial or genital lesions does not rule out the possibility of active HSV infection.
 ...
PMID:Generalized herpes simplex virus infection in an immunocompromised patient--report of a case and review of the literature. 1590 Nov 33

Herpes simplex viruses (HSV) are highly pervasive pathogens in the human host with a seroconversion rate upwards of 60% worldwide. HSV type 1 (HSV-1) is associated with the disease herpetic stromal keratitis, the leading cause of infectious corneal blindness in the industrialized world. Individuals suffering from genital herpes associated with HSV type 2 (HSV-2) are found to be two- to threefold more susceptible in acquiring human immunodeficiency virus (HIV). The morbidity associated with these infections is principally due to the inflammatory response, the development of lesions, and scarring. Chemokines have become an important aspect in understanding the host immune response to microbial pathogens due in part to the timing of expression. In this paper, we will explore the current understanding of chemokine production as it relates to the orchestration of the immune response to HSV infection.
 ...
PMID:Herpes simplex virus and the chemokines that mediate the inflammation. 1657 Aug 56

Previous studies have shown that peptides containing the protein transduction domain (PTD) of the human immunodeficiency virus tat protein (GRKKRRQRRR) were effective inhibitors of herpes simplex virus type 1 (HSV-1) entry (H. Bultmann and C. R. Brandt, J. Biol. Chem. 277:36018-36023, 2002). We now show that the addition of a single cysteine residue to the C terminus of the TAT PTD (TAT-C peptide) improves the antiviral activity against HSV-1 and HSV-2. The principle effect of adding the cysteine was to enable the peptide to inactivate virions and to induce a state of resistance to infection in cells pretreated with peptide. The TAT-C peptide acted extracellularly, immediately blocked entry of adsorbed virus, prevented VP16 translocation to the nucleus, and blocked syncytium formation and cell-cell spread. Thus, TAT-C peptides are fusion inhibitors. The induction of the resistance of cells to infection was rapid, recovered with a half-life of 5 to 6 h, and could be reinduced by peptide treatment. TAT-C bound to heparan sulfate but was a poor competitor for viral attachment. The antiviral activity depended on the net positive charge of the peptide but not on chirality, and a free sulfhydryl group was not essential for antiviral activity because TAT-C dimers were at least as effective as monomers. The unique combination of antiviral activities and low toxicity combine to make TAT-C a strong candidate for further development as a drug to block HSV infection.
 ...
PMID:Addition of a C-terminal cysteine improves the anti-herpes simplex virus activity of a peptide containing the human immunodeficiency virus type 1 TAT protein transduction domain. 1726 27

Molecular umbrella compounds may function as novel topical microbicides to prevent human immunodeficiency virus (HIV) and herpes simplex virus (HSV) infections. In a preliminary structure-activity investigation, one umbrella compound, designated Spm8CHAS, was identified which inhibited both HIV and HSV infections with no cellular toxicity. The objectives of the current studies were to define its spectrum of antiviral activity, characterize its mechanism of action, and explore the possibility of combining Spm8CHAS with HIV-specific reverse transcriptase inhibitors. Spm8CHAS inhibited infections by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical tissue explants exposed to HIV-1(BaL) in the presence of Spm8CHAS were completely protected (50% inhibitory concentration [IC(50)], 13.6 microg/ml), and transfer of virus to target T cells via migratory cells was abolished (IC(50), 3.8 microg/ml). Spm8CHAS inhibited HSV-2 infection of epithelial cells 10,000-fold if present throughout the infection. Notably, adding Spm8CHAS to cultures following HSV entry significantly reduced viral infection, indicating that the drug also acts postentry. Subsequent studies indicated that Spm8CHAS blocks cell-to-cell spread of HSV. Confocal microscopy using a fluorescently labeled analog of Spm8CHAS demonstrated that this conjugate crosses the plasma cell membrane and is transported to the nucleus. Combinations of Spm8CHAS with UC-781 or 9-[R-2-(phosphonylmethoxy)propyl] adenine monohydrate in vitro exhibited additive anti-HIV activity with preserved anti-HSV activity. The abilities of Spm8CHAS to inhibit primary isolates of HIV, block HSV infection postentry, and cross cell membranes support the development of a combination microbicide containing Spm8CHAS with an HIV-specific reverse transcriptase inhibitor to prevent both HIV and HSV infections by multiple mechanisms.
 ...
PMID:Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections. 1749 78

Secretory leukocyte protease inhibitor (SLPI), an anti-inflammatory mediator of mucosal immunity, inhibits human immunodeficiency virus (HIV) and herpes simplex virus (HSV) in cell culture. Epidemiological studies demonstrate that higher concentrations of SLPI in mucosal secretions are associated with a reduced risk of HIV transmission. The current studies were designed to test the hypothesis that HSV triggers a loss of SLPI to evade innate immunity and that this response may contribute to the increased risk of HIV infection in the setting of HSV infection. Exposure of human cervical epithelial cells to HSV-1 or HSV-2, but not HIV or vesicular stomatitis virus, triggered a significant and sustained reduction in SLPI levels. The reduction persisted when cells were infected in the presence of acyclovir but not following infection with UV-inactivated virus, indicating that viral gene expression, but not replication, is required. Reverse transcriptase PCR studies demonstrated that the loss of SLPI is mediated by downregulation of gene expression. SLPI downregulation was associated with activation of NF-kappaB signaling pathways and upregulation of proinflammatory cytokines, consistent with the known inhibitor effects of SLPI on NF-kappaB pathways. The downregulation mapped to viral early-gene expression, as variants impaired in expression of the ICP4 or ICP0 immediate-early gene failed to downregulate SLPI or activate NF-kappaB. Together, these results identify a novel role for HSV immediate-early-gene expression in regulating mucosal immune responses.
 ...
PMID:Herpes simplex virus downregulates secretory leukocyte protease inhibitor: a novel immune evasion mechanism. 1866 8

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.
 ...
PMID:Thymoma, immunodeficiency, and herpes simplex virus infections. 1926 57

Old World monkey TRIM5alpha 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 TRIM5alpha proteins can restrict herpes simplex virus (HSV) infection. To define the effect of TRIM5alpha on HSV replication, we examined HSV infection in HeLa cell lines that stably express simian and human orthologs of TRIM5alpha proteins. We demonstrated that several simian TRIM5alpha proteins can restrict HSV replication, with the TRIM5alpha 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. TRIM5alpha is likely to inhibit HSV at the early stage of infection; however, at later times of infection, the levels of TRIM5alpha are significantly decreased. Thus, some TRIM5alpha proteins exhibit antiviral effects that extend beyond retroviral infections, but HSV may be able to reduce this restriction by reducing TRIM5alpha levels during the later phases of virus replication. Our results also argue that TRIM5alpha 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.
 ...
PMID:Simian TRIM5alpha proteins reduce replication of herpes simplex virus. 2006 Sep 96


<< Previous 1 2 3 4 5 Next >>