Herpes simplex virus (HSV) infection triggers apoptosis in infected cells. However, proteins synthesized later in infected cells prevent apoptotic cell death from ensuing. In vivo data showing that apoptosis accompanies herpes stromal keratitis and encephalitis suggest that apoptotic modulation plays a role in the development of herpetic disease. Tremendous progress ...

Viral infection is detected by the host innate immune system. Innate immune cells such as dendritic cells and macrophages detect nucleic acids derived from viruses through pattern recognition receptors (PRRs). Viral recognition by PRRs initiates the activation of signaling pathways that lead to production of type I interferon and inflammatory ...

Negative immune regulation can result in the poor control of virus replication in chronic infections but is probably important to prevent tissue damage from chronic immune activation. Three recent studies have shown that programmed cell death (PD)-1 expression on T cells correlates with viral load in HIV infection, and that ...

Regulatory T cells (Treg) play a key role in the impaired immune response that is typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in the mechanism that is responsible for this impaired immune response, the effect of viral load reduction resulting from treatment with the ...

Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway. In order to complete their life cycles, viruses must modulate the host IFN-mediated immune response. The K3 and K5 proteins of a human tumor-inducing herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), have ...

Crimean-Congo hemorrhagic fever virus (CCHFV) is an etiological agent of a disease with mortality rates in patients averaging 30%. The disease is characterized by fever, myalgia, and hemorrhage. Mechanisms underlying the hemorrhage have to our knowledge not been elucidated for CCHFV. Possibly, a direct or indirect viral effect on tight ...

Human immunodeficiency virus (HIV) infection causes chronic progressive immunodeficiency and immune dysregulaton. Although simple depletion of the major target of HIV infection, the CD4+ T cell, can explain much of the immunosuppression seen, there are multiple other factors contributing to the immune dysregulation. CD4+ T-cell depletion induces a range of ...

Feline infectious peritonitis virus (FIPV) positive cells are present in pyogranulomas and exudates from cats with FIP. These cells belong mainly to the monocyte/macrophage lineage. How these cells survive in immune cats is not known. In this study, FIPV positive cells were isolated from pyogranulomas and exudates of 12 naturally ...

Clinical and experimental evidence indicates that human herpesvirus 6 (HHV-6) can interfere with the function of the host immune system through a variety of mechanisms. Both HHV-6A and B can infect, either productively or nonproductively, several types of immune cells. The primary target for HHV-6 replication, both in vitro and ...

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be risk factors for a systemic inflammatory syndrome in viral infections. Innate immune cells are likely to represent the preferential targets for the deleterious effects of NSAIDs in patients with viral infections. We therefore examined whether various classes of NSAIDs could selectively inhibit ...

Microglial cells and astrocytes are glial cell types that perform distinct functions and generate innate immune responses to counter invading pathogens. Herpes simplex virus 1 (HSV-1) is a neurotropic virus that is capable of causing severe, necrotizing encephalitis. HSV-1 infects both of these glial cell types. Microglial cells undergo an ...

Adenoviruses (Ads) cause acute and persistent infections. The genome of Ads has five early transcription units that are the first viral genes expressed during an active infection. The Early Region 1A (E1A) gene of the adenovirus genome is crucial for adenovirus transformation of the host cell. Ads E1A block some ...

Vaccinia virus (VV) is an effective vaccine and vector but has evolved multiple mechanisms for evading host immunity. We characterized the interactions of VV (TianTan and New York City Board of Health strains) with human gammadelta T cells because of the role they play in immune control of this virus. ...

Adenoviral infections represent a major cause of morbidity and mortality following haematopoietic stem cell transplantation. Current anti-viral agents are virostatic and it is evident that elimination of adenovirus (ADV) infection is only achieved by recovery of cellular immunity. Using an interferon-gamma (IFN-gamma) secretion and capture assay to isolate ADV-specific T ...

Macrophages play a central role in the pathogenesis of atherosclerosis and are also a host for a number of viruses, most importantly, HIV. Many viruses, including HIV, require cholesterol for their replication and as a structural element. Cholesterol also plays a pivotal role in innate antiviral immune responses. Although impairing ...

We used a porcine microarray containing 2,880 cDNAs to investigate the response of macrophages to infection by a virulent African swine fever virus (ASFV) isolate, Malawi LIL20/1. One hundred twenty-five targets were found to be significantly altered at either or both 4 h and 16 h postinfection compared with targets ...

Lung pathology observed during influenza infection is due to direct damage resulting from viral replication and bystander damage caused by overly exuberant antiviral immune mechanisms. In the absence of universally effective vaccines and antiviral therapies, knowledge of the cellular components required for immune containment of influenza is essential. ICOS is ...

T cells are an essential component of the immune response against herpes simplex virus (HSV) infection. We previously reported that incubation of T cells with HSV-infected fibroblasts inhibits subsequent T cell antigen receptor signal transduction. In the current study, we found that incubation of T cells with HSV-infected fibroblasts also ...

BACKGROUND: The aim of this study was to evaluate the site-specific immunoregulatory mechanisms against viral infection in human Fallopian tubes. METHODS: We therefore investigated the effects of double-stranded RNA (dsRNA) on the production of interleukin (IL)-6, IL-8 and granulocyte chemotactic protein-2 (GCP-2) by cultured oviductal epithelial cells (OECs) using enzyme-linked ...

Persistent viral infections are a major health concern. One obstacle inhibiting the clearance of persistent infections is functional inactivation of antiviral T cells. Although such immunosuppression occurs rapidly after infection, the mechanisms that induce the loss of T-cell activity and promote viral persistence are unknown. Herein we document that persistent ...

The mechanisms of liver injury in hepatitis B virus (HBV) infection are defined to be due not to the direct cytopathic effects of viruses, but to the host immune response to viral proteins expressed by infected hepatocytes. We showed here that transfection of mammalian cells with a replicative HBV genome ...

Double-stranded RNA (dsRNA) is a common virus-associated molecular pattern and a potent inducer of antiviral responses in many organisms. While it is clear that the specific RNA interference (RNAi) response, a phenomenon triggered by dsRNA, serves antiviral functions in invertebrates, innate (non-specific) antiviral immune reactions induced by dsRNA (e.g. the ...

Alcohol tinctures prepared from aged Echinacea roots are typically taken for preventing or treating upper respiratory infections, as they are purported to stimulate immunity in this context. The effects of long-term (> 1 year) dry storage on the capabilities of Echinacea spp. roots from mature individuals to modulate cytokine production ...

Bovine viral diarrhea virus (BVDV), which is classified in the genus Pestivirus, family Flaviviridae, can be divided into two biotypes according to its ability to induce a cytopathic effect in tissue culture cells. The mechanisms through which cytopathogenic (cp) BVDV induces cell death and non-cytopathogenic (ncp) BVDV causes persistent infection ...

Human immunodeficiency virus-1 (HIV-1) neuroinvasion occurs early (during period of initial viremia), leading to infection of a limited amount of susceptible cells with low CD4 expression. Protective cellular and humoral immunity eliminate and suppress viral replication relatively quickly due to peripheral immune responses and the low level of initial central ...

Viral infection induces the production of interleukin (IL)-1beta and IL-18 in macrophages through the activation of caspase-1, but the mechanism by which host cells sense viruses to induce caspase-1 activation is unknown. In this report, we have identified a signaling pathway leading to caspase-1 activation that is induced by double-stranded ...

Epstein-Barr virus (EBV) establishes a persistent infection in the human host and is associated with a variety of human cancers. Persistent infection results from a balance between the host immune response and viral immune evasion mechanisms. EBV infection is controlled initially by the innate immune response and later by T-cell-mediated ...

Following integration of human papillomavirus (HPV) into the host genome, overexpression of the viral oncogenes E6 and E7 requires loss of the transcriptional repressor functions of E2. A key step in HPV-related carcinogenesis is therefore clearance of residual viral episomes, which encode E2. As spontaneous loss of HPV-16 episomes in ...

Determining which antigen must be included in AIDS vaccines to confer maximum protection is of utmost importance. In primate models, vaccines consisting of or including accessory viral proteins have yielded conflicting results. We investigated the protective potential of the accessory protein ORF-A of feline immunodeficiency virus (FIV) in cats. All ...

The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a formidable battle horse for the study of viral immunology, as well as viral persistence and associated diseases. Investigations with LCMV have uncovered basic mechanisms by which viruses avoid elimination by the host adaptive immune response. In this study we show that ...

Many autoimmune diseases are thought to be precipitated by viral infections. In this issue of the JCI, Lang et al. demonstrate that, in a mouse model of autoimmune hepatitis, viral infections not only trigger expansion of self-reactive T cells but also activate antigen-presenting cells through TLR stimulation (see the related ...

2'-5'oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes involved in the function of interferons (IFNs), a family of cytokines participating in innate immunity against viruses and other microbial pathogens. Upon binding with its activator, 5'-phosphorylated, 2'-5' linked oligoadenylates (2-5A), RNase L degrades single-stranded viral and cellular RNAs ...

Understanding basic antiviral mechanisms in vertebrates is essential for developing methods to enhance antiviral responses and promote human and animal health. In fish these antiviral mechanisms are poorly understood, but are important to understand because of the devastating impact of viral diseases on aquaculture. Therefore, the antiviral responses of a ...

The antiviral and antitumor functions of RNase L Abstract By Geqiang Li RNase L is an endoribonuclease that functions in the molecular pathways of interferon (IFN) action against viral infections. Although the pro-apoptotic activity of RNase L is well known, how RNase L activation during viral infection leads to apoptosis ...

While the interferon (IFN)-inducible double-stranded RNA (dsRNA)-dependent protein kinase PKR is reported to initiate apoptosis in some instances, the mechanism by which diverse stress stimuli activate PKR remains unknown. Now we report that RAX, the only known cellular activator for PKR, initiates PKR activation in response to a broad range ...

Several viruses, including human cytomegalovirus (HCMV), encode proteins that colocalize with a cellular subnuclear structure known as ND10. Since only viral DNA deposited at ND10 initiates transcription, ND10 structures were hypothesized to be essential for viral replication. On the other hand, interferon treatment induces an up-regulation of ND10 structures and ...

A number of investigations have linked respiratory viral infections and the intensity and subsequent exacerbation of asthma through host response mechanisms. For example, it is likely that the immune-inflammatory response to respiratory syncytial virus can cause a predisposition toward an intense inflammatory reaction associated with asthma, and adenovirus might cause ...

The regulation of host-mediated apoptosis by the E6 and E7 oncoproteins has garnered attention because it is believed to be an important strategy employed by high-risk (HR)-human papillomaviruses (HPVs) to evade immune surveillance. Additionally, the revelation that E5 can protect cells from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis suggests ...

The role of Epstein-Barr virus (EBV) lytic cycle gene expression in lymphocytes in the pathogenesis of EBV-associated diseases is incompletely understood. The ability to physically separate lytically induced from latently infected cells from the same population and to examine them in parallel would significantly enhance understanding of the viral, cellular, ...

In recent years, regulatory T cells have received increased attention for their role in immune responses to microbial infections. The list of microbial pathogens associated with regulatory T cell responses is growing rapidly and includes bacteria, viruses, parasites, and fungi. As the biology of regulatory T cells is revealed, we ...

A historically based literature review of the relationship between acute viral myocarditis and the subsequent development of a dilated cardiomyopathic state is presented. A strong emphasis on a state of definitional ambiguity in the literature as regards the timing of the myopathic state following a viral infection is noted, i.e. ...

Mononuclear phagocytes (MP; bone marrow monocyte-derived macrophages, histiocytes, alveolar macrophages, Kupffer cells, perivascular macrophages, and microglia) function as sentry and surveillance cells by acting as debris scavengers, killers of microbial pathogens, and regulators of immune responses. Interestingly, these same cells are reservoirs and vehicles of dissemination for the human immunodeficiency ...

Apoptosis is a highly regulated programmed cell death process which is activated during normal development and by various stimuli, such as viral infection, which disturb cellular metabolism and physiology. That herpes simplex virus type 1 (HSV-1) induces apoptosis but then prevents its killing of infected cells is well-established. However, little ...

Viral infection of mammalian cells activates an innate antiviral immune response characterized by production of interferon and subsequent enhanced transcription of interferon–stimulated genes important for antiviral defense. Cells recognize viral infection through various pathogen–associated molecular patterns, of which dsRNA seems to be the most important. In mammals, several gene products ...

To develop an animal model of Kaposi sarcoma-associated herpesvirus (KSHV) infection uniquely suited to evaluate longitudinal patterns of viral gene expression, cell tropism, and immune responses, we injected NOD/SCID mice intravenously with purified virus and measured latent and lytic viral transcripts in distal organs over the subsequent 4 months. We ...

Substantial evidence implicates common respiratory viral infections in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Children who experience recurrent virally induced wheezing episodes during infancy are at greater risk for developing asthma. In addition, respiratory viral infections are a major trigger for acute exacerbations of both asthma ...

Human cytomegalovirus (HCMV) employs a variety of strategies to modify or evade the host immune response, and natural killer (NK) cells play a crucial role in controlling cytomegalovirus infections in mice and humans. Activation of NK cells through the receptor NKG2D/DAP10 leads to killing of NKG2D ligand-expressing cells. We have ...

Interferons were the first of the anti-viral innate immune modulators to be characterized, initially characterized solely as anti-viral proteins [reviewed in Le Page, C., Genin, P., Baines, M.G., Hiscott, J., 2000. Inteferon activation and innate immunity. Rev. Immunogenet. 2, 374-386]. As we have progressed in our understanding of the interferons ...

Cross-species infections are responsible for the majority of emerging and re-emerging viral diseases. However, little is known about the mechanisms that restrict viruses to a certain host species, and the factors viruses need to cross the species barrier and replicate in a different host. Cytomegaloviruses (CMVs) are representatives of the ...

Since previous results showed that interleukin 8 (IL-8) was induced in rainbow trout (Oncorhynchus mykiss) in response to viral hemorrhagic septicemia virus (VHSV) infection, we have cloned IL-8 in an expression vector (pIL8+) and studied its possible adjuvant effect on the early response to a VHSV immunization model, focusing on ...