Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “viral pathogenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1996

Effect of E2 envelope glycoprotein cytoplasmic domain mutations on Sindbis virus pathogenesis.

The cytoplasmic domain of the E2 envelope glycoprotein is important in Sindbis virus assembly, but little is known about its role in the pathogenesis of Sindbis virus encephalitis. To investigate its role in viral pathogenesis, we constructed six recombinant viruses containing site mutations in the E2 cytoplasmic domain, using the neurovirulent background strain, TE12. Our findings demonstrate that the E2 cytoplasmic domain is a determinant of Sindbis virus growth and neurovirulence in suckling mice as well as persistent infection in weanling scid mice. They also suggest that the tyrosine, serine, or threonine residues are not essential for replication in mouse brain or anti-E2 monoclonal antibody-mediated restriction of Sindbis virus replication.

Alphavirus Infections↗
PubMed2003

Antibodies to Tat and Vpr in the GRIV cohort: differential association with maintenance of long-term non-progression status in HIV-1 infection.

The HIV-1 regulatory protein Tat and the accessory protein Vpr are thought to stimulate viral replication and contribute to viral pathogenesis as extracellular proteins. Humoral immune responses to these early viral proteins may therefore be beneficial. We examined serum anti-Tat and anti-Vpr IgG by ELISA in the GRIV cohort of HIV-1 seropositive slow/non-progressors (NP) and fast-progressors (FP), and in seronegative controls. Based on information obtained during a brief follow-up period (median = 20 months), NPs were sub-grouped as those maintaining non-progression status and therefore stable (NP-S), and those showing signs of disease progression (NP-P). As the primary comparison, initial serum anti-Tat and anti-Vpr IgG (prior to follow-up) were analyzed in the NP sub-groups and in FPs. Anti-Tat IgG was significantly higher in stable NP-S compared to unstable NP-P (P = 0.047) and FPs (P < 0.0005); the predictive value of higher anti-Tat IgG for maintenance of non-progression status was 92% (P = 0.029). In contrast, no-difference was observed in anti-Vpr IgG between NP-S and NP-P, although both were significantly higher than FPs (P </= 0.001). Serum anti-Tat IgG mapped to linear epitopes within the amino-terminus, the basic domain and the carboxy-terminal region of Tat in stable NP-S. Similar epitopes were identified in patients immunized with the Tat-toxoid in a Phase I study in Milan. High titer serum anti-Tat IgG from both GRIV and Milan cohorts cross-reacted in ELISA with Tat from diverse viral isolates, including HIV-1 subtype-E (CMU08) and SIVmac251 Tat; a correlation was observed between anti-Tat IgG titers and cross-reactivity. These results demonstrate that higher levels of serum anti-Tat IgG, but not anti-Vpr IgG, are associated with maintenance of non-progression status in HIV-1 infection. Evidence that vaccination with the Tat toxoid induces humoral immune responses to Tat similar to those observed in stable non-progressors is encouraging for vaccine strategies targeting Tat.

Cohort Studies↗
PubMed2001

SIV cardiomyopathy in non-human primates.

While cardiac myocytes are not generally considered conventional cellular targets of retroviral infection with HIV-1, the increasing recognition of AIDS related cardiomyopathy has raised important questions as to the viral pathogenesis. Our laboratory has explored the role of simian immunodeficiency viral (SIV) infection in non-human primates as a suitable large-animal model to examine cardiac involvement. Our data suggest that in the presence of inflammatory myocarditis, SIV is localized to CD4 bearing inflammatory cells and not cardiac myocytes, suggesting that the heart may be an innocent bystander in AIDS cardiomyopathy.

Animals↗
PubMed2000

Plant DNA viruses and gene silencing.

Gene silencing is a multifaceted phenomenon leading to propagative down-regulation of gene expression. Gene silencing, first observed in plants containing transgenes, can operate both at the transcriptional and post-transcriptional levels. Silencing effects can be triggered by nuclear transgenes and by cytoplasmic RNA viruses, and it can be propagated between these elements and endogenous plant genes that share sequence homology. Although some aspects of gene silencing are becoming better understood, little is yet known about the relationship between nuclear and cytoplasmic events. Plant DNA viruses-- both the ssDNA geminiviruses and the reverse-transcribing pararetroviruses-- have properties with the potential to initiate gene silencing in the nucleus and in the cytoplasm. Characteristics include production of multiple copies of viral DNA genomes in the nucleus, illegitimate integration of viral DNA into host chromosomes mimicking transgene transformation, and generation of abundant viral RNAs in the cytoplasm. Evidence is emerging that geminiviruses and plant pararetroviruses can interact with the gene silencing system either from introduced DNA constructs or during viral pathogenesis. Some observations suggest there are complex relationships between DNA viral activity, transcriptional and post-transcriptional gene silencing mechanisms. DNA viruses also have properties consistent with an ability to counteract the plant silencing response. In this article, features of plant DNA viruses are discussed in relation to gene silencing phenomena, and the prospects for understanding the interaction between nuclear and cytoplasmic silencing processes.

DNA Viruses↗
PubMed2004

Advances in laboratory testing for HIV.

In 2004, the diagnosis of established human immunodeficiency virus (HIV) infection can be made with close to 100% assurity. The extraordinarily engineered performances of HIV-screening assays are unprecedented. The well-established confirmatory tests performed by well-versed laboratories using criteria that are well understood in order to interpret the results of these tests give highly accurate outcomes of diagnostic testing strategies. Furthermore, the ability to monitor the progress of the infection and the viral pathogenesis is possible through the use of tests that quantify viral load or the peripheral CD4+ T-cells and other lymphocyte sub-type levels. Newer laboratory testing mechanisms, such as assessment of reverse transcriptase activity and sophisticated cell staining and flow cytometric analyses, have been used to map disease processes and progress on a research level and may be used in future to fine-tune therapy and to follow disease progression in even greater detail. Regulation of all HIV tests is of the highest level in Australia. In-house tests will be expected to conform to the levels specified for commercially produced tests.

Clinical Laboratory Techniques↗
PubMed1990

Respiratory viruses interfere with bacteriologic response to antibiotic in children with acute otitis media.

Fifty-eight infants and children with acute otitis media were prospectively studied for bacterial and viral pathogenesis and response to antibiotic therapy. Tympanocentesis for bacterial and viral cultures of middle ear fluids (MEF) was done before and 2-4 days after beginning treatment. Patients were followed until the end of antibiotic course. Bacteria were cultured from the preantibiotic MEF in 43 cases (74%). Viruses were cultured from the preantibiotic MEF in 11 cases (19%); all of these MEFs also contained bacterial pathogens. A significantly higher proportion of patients with both virus and bacteria (50%) failed to respond with clearing of bacteria 2-4 days into therapy compared with the group with bacteria alone (13%). The patients with persistently positive viral cultures of the MEF seemed to have purulent otitis of longer duration. Presence of virus in the MEF may interfere with bacteriologic and clinical responses to antibiotic. The mechanism of interference deserves further investigation.

Acute Disease↗
PubMed1997

Histopathology and pathobiology of hepatotropic virus-induced liver injury.

The present report concerns current knowledge regarding immunopathogenesis that can be applied in the interpretation of histopathological changes in acute and chronic viral hepatitis. The histopathological features of viral hepatitis have not been changed and light microscopic examination remains essential for making a diagnosis and classification of chronic hepatitis and for the provision of objective parameters on grading and staging. However, new understanding and knowledge of viral pathogenesis, host immune responses, the biological behaviour of the causative viral agents and, in particular, viral interference in multiple hepatotropic viral infections must be taken into consideration in the interpretation of histopathological and immunopathological findings of liver tissues. This report also presents some histopathological analyses on multiple hepatotropic viral infections. It can be concluded that the diagnostic histological criteria for acute hepatitis remain applicable in such settings. However, the cause of acute flare up in chronic hepatitis could not be determined without clinical, virological and serological information. Routine histopathology cannot distinguish a new infection from an acute exacerbation due to a high level of viral replication or mutant virus. A repertoire of immunocytochemical stainings for viral antigens is helpful, but caution must be exercised in suggesting a specific viral aetiology due to the fact that suppression of pre-existing viral antigens can be pronounced when the new or concurrent infection is hepatitis C virus related.

Animals↗
PubMed1994

Soluble interleukin-2 receptor monitoring during bacterial and viral infections in liver transplant recipients: a comparative evaluation.

We evaluated the significance of serial sIL-2R serum levels as a differential marker of immune activation during bacterial versus viral infections in liver transplant recipients. A comparative evaluation of sIL-2R levels was performed in 76 liver transplant recipients (51 pediatric and 27 adult) during bacterial versus viral infections at 7 days prior to infection diagnosis (DAY-7), the day of diagnosis (DAY 0), peak sIL-2R level and at the end of therapy (END). There were no significant elevations at any time point during bacterial infections in either adult or pediatric transplant recipients. However, adult recipients demonstrated significant elevations during viral infections when comparing DAY-7 to PEAK (3840 +/- 830 vs 7225 +/- 2814 p = 0.03), with PEAK levels significantly higher during viral versus bacterial infections in this population (7225 +/- 2814 vs 4195 +/- 1819). Pediatric recipients demonstrated similar increases in sIL-2R serum levels during viral infections from DAY-7 to PEAK (4932 +/- 887 vs 11323 +/- 2794 p = 0.0012). Significant decreases from PEAK to END were noted during viral infections in both adult and pediatric recipients (7225 +/- 2814 vs 2911 +/- 1376 p = 0.01 and 11323 +/- 2794 vs 5214 +/- 2403 p = 0.006). Pediatric recipients had higher mean sIL-2R levels than adult recipients at all time points during viral infections. In conclusion, significant elevations in mean sIL-2R serum levels were observed during viral but not bacterial infections in pediatric and adult liver transplant recipients. This suggests that serial sIL-2R monitoring is a valuable immunologic marker of viral pathogenesis and may be useful in monitoring the progression of viral infections as well as response to antiviral therapy.

Adolescent↗
PubMedDate not supplied

[Anti-retroviral treatment of HIV infection in the child].

The treatment of HIV infection has changed recently in children and adults. The new guidelines are based on a better knowledge of viral pathogenesis, control of the infection and treatment effectiveness using the viral load, and the availability of new antiretroviral drugs. Cumulative clinical experience and the results of therapeutic trials suggest that treatment should begin early, before immune system disorders occur, in order to prevent viral dissemination and neurological involvement. Combined therapy with at least two drugs is recommended, although triple therapy with two inhibitors of inverse transcriptase and a protease inhibitor is advised as a way to delay the appearance and selection of resistant viral strains. Given the complexity of these treatment guidelines, the side effects of antiretroviral agents, and drug interactions with many medications, meticulous and detailed information for the family and child is necessary to ensure compliance and guarantee therapeutic effectiveness. The object should be to achieve an individualized and rational therapy that is adapted to the childís schedule and uses the drug formulation that the child best tolerates. The are reasons for optimism because new drugs are being developed and many of our patients will undoubtedly benefit from them. However, it should not be forgotten that many children with HIV infection in the third world cannot receive treatment for social and economic reasons.

AIDS Dementia Complex↗
PubMed1996

Bc1-2 protects mice against fatal alphavirus encephalitis.

Virus-induced apoptosis has been well characterized in vitro, but the role of apoptosis in viral pathogenesis is not well understood. The suicide of a cell in response to viral infection is postulated to be an important host defense for the organism, leading to a reduction in its total viral burden. However, virus-induced death of nonregenerating cells in the central nervous system may be detrimental to the host. Therefore, to investigate the role of apoptosis in the pathogenesis of fatal encephalitis, we constructed a recombinant alphavirus chimera that expresses the antiapoptotic gene, bcl-2, in virally infected neural cells. Infection of neonatal mice with the alphavirus chimera expressing human bcl-2 [Sindbis virus (SIN)/bcl-2] resulted in a significantly lower mortality rate (7.5%) as compared with infection with control chimeric viruses containing a chloramphenicol acetyltransferase (CAT) reporter gene (SIN/CAT) (78.1%) or bcl-2 containing a premature stop codon (SIN/bcl-2stop) (72.1%) (P < 0.001). Viral titers were reduced 5-fold 1 day after infection and 10-fold 6 days after infection in the brains of SIN/bcl-2-infected mice as compared to SIN/CAT or SIN/bcl-2stop-infected mice. In situ end labeling to detect apoptotic nuclei demonstrated a reduction in the number of foci of apoptotic cells in the brains of mice infected with SIN/bcl-2 as compared with SIN/bcl-2stop. The reduction in apoptosis was associated with a reduction in the number of foci of cells expressing alphavirus RNA. Thus, the antiapoptotic gene, bcl-2, suppresses viral replication and protects against a lethal viral disease, suggesting an interaction between cellular genetic control of viral replication and cell death.

Alphavirus Infections↗
PubMed1997

Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor.

Hepatitis C virus (HCV) core protein is a multifunctional protein. We examined whether it can interact with cellular proteins, thus contributing to viral pathogenesis. Using the HCV core protein as a bait to screen a human liver cDNA library in a yeast two-hybrid screening system, we have isolated several positive clones encoding cellular proteins that interact with the HCV core protein. Interestingly, more than half of these clones encode the cytoplasmic domain of lymphotoxin-beta receptor (LT betaR), which is a member of the tumor necrosis factor receptor family. Their binding was confirmed by in vitro glutathione S-transferase fusion protein binding assay and protein-protein blotting assay to be direct and specific. The binding sites were mapped within a 58-amino-acid region of the cytoplasmic tail of LT betaR. The binding site in the HCV core protein was localized within amino acid residues 36 to 91 from the N terminus, corresponding to the hydrophilic region of the protein. In mammalian cells, the core protein was found to be associated with the membrane-bound LT betaR. Since the LT betaR is involved in germinal center formation and developmental regulation of peripheral lymphoid organs, lymph node development, and apoptotic signaling, the binding of HCV core protein to LT betaR suggests the possibility that this viral protein has an immunomodulating function and may explain the mechanism of viral persistence and pathogenesis of HCV.

Binding Sites↗
PubMed1998

Involvement of NF-AT in type I human T-cell leukemia virus Tax-mediated Fas ligand promoter transactivation.

Human T-cell leukemia virus type I (HTLV-I)-infected T-cells constitutively express surface Fas ligand (FasL), which may serve as a mechanism of viral pathogenesis. HTLV-I induces transcription of FasL gene through the viral transactivator Tax, although the underlying molecular mechanism remains unclear. In the present study, we have analyzed both the cis-activating element and transactivating factors involved in Tax activation of the FasL promoter. We show that the 486-base pair upstream region of the human FasL gene is sufficient for Tax-mediated transactivation in Jurkat T-cells. Interestingly, a palindromic DNA sequence (GGAAACTTCC) covering the consensus NF-ATp binding site (GGAAA), is required for Tax activation of FasL promoter. The involvement of NF-AT in this transactivation event is suggested by the finding that Tax fails to activate the FasL promoter in a Jurkat T-cell line defective in capacitative calcium entry, a signaling mechanism involved in NF-AT activation. Furthermore, activation of FasL promoter by Tax is largely attenuated in the nonlymphoid F9 embryonal and COS kidney cells deficient in NF-ATp expression. DNA-protein interaction assays reveal that the NF-AT-like motif in the FasL promoter is bound by both NF-ATp and NF-AT4 in Jurkat T-cells expressing Tax. The binding of NF-ATp, although not NF-AT4, to this enhancer also occurs along with HTLV-I-mediated infection of human peripheral blood T-cells. Furthermore, exogenously transfected NF-ATp binds to the NF-AT-like enhancer and participates in Tax-mediated FasL promoter transactivation. These results suggest an important role for proteins of the NF-AT family in HTLV-I Tax-mediated FasL gene transactivation.

Base Sequence↗
PubMed2006

Attenuation of herpes simplex virus neurovirulence with picornavirus cis-acting genetic elements.

Viral pathogenesis depends on a suitable milieu in target host cells permitting viral gene expression, propagation, and spread. In many instances, viral genomes can be manipulated to select for propagation in certain tissues or cell types. This has been achieved for the neurotropic poliovirus (PV) by exchange of the internal ribosomal entry site (IRES), which is responsible for translation of the uncapped plus-strand RNA genome. The IRES of human rhinovirus type 2 (HRV2) confers neuron-specific replication deficits to PV but has no effect on viral propagation in malignant glioma cells. We report here that placing the critical gamma(1)34.5 virulence genes of herpes simplex virus type 1 (HSV) under translation control of the HRV2 IRES results in neuroattenuation in mice. In contrast, IRES insertion permits HSV propagation in malignant glioma cell lines that do not support replication of HSV recombinants carrying gamma(1)34.5 deletions. Our observations indicate that the conditions for alternative translation initiation at the HRV2 IRES in malignant glioma cells differ from those in normal central nervous system (CNS) cells. Picornavirus regulatory sequences mediating cell type-specific gene expression in the CNS can be utilized to target cancerous cells at the level of translation regulation outside their natural context.

Animals↗
PubMed1998

Role of the SH3-ligand domain of simian immunodeficiency virus Nef in interaction with Nef-associated kinase and simian AIDS in rhesus macaques.

The nef gene of the human and simian immunodeficiency viruses (HIV and SIV) is dispensable for viral replication in T-cell lines; however, it is essential for high virus loads and progression to simian AIDS (SAIDS) in SIV-infected adult rhesus macaques. Nef proteins from HIV type 1 (HIV-1), HIV-2, and SIV contain a proline-Xaa-Xaa-proline (PxxP) motif. The region of Nef with this motif is similar to the Src homology region 3 (SH3) ligand domain found in many cell signaling proteins. In virus-infected lymphoid cells, Nef interacts with a cellular serine/threonine kinase, designated Nef-associated kinase (NAK). In this study, analysis of viral clones containing point mutations in the nef gene of the pathogenic clone SIVmac239 revealed that several strictly conserved residues in the PxxP region were essential for Nef-NAK interaction. The results of this analysis of Nef mutations in in vitro kinase assays indicated that the PxxP region in SIV Nef was strikingly similar to the consensus sequence for SH3 ligand domains possessing the minus orientation. To test the significance of the PxxP motif of Nef for viral pathogenesis, each proline was mutated to an alanine to produce the viral clone SIVmac239-P104A/P107A. This clone, expressing Nef that does not associate with NAK, was inoculated into seven juvenile rhesus macaques. In vitro kinase assays were performed on virus recovered from each animal; the ability of Nef to associate with NAK was restored in five of these animals as early as 8 weeks after infection. Analysis of nef genes from these viruses revealed patterns of genotypic reversion in the mutated PxxP motif. These revertant genotypes, which included a second-site suppressor mutation, restored the ability of Nef to interact with NAK. Additionally, the proportion of revertant viruses increased progressively during the course of infection in these animals, and two of these animals developed fatal SAIDS. Taken together, these results demonstrated that in vivo selection for the ability of SIV Nef to associate with NAK was correlated with the induction of SAIDS. Accordingly, these studies implicate a role for the conserved SH3 ligand domain for Nef function in virally induced immunodeficiency.

Animals↗
PubMed2004

Nitric oxide as an endogenous mutagen for Sendai virus without antiviral activity.

Nitric oxide (NO) may affect the genomes of various pathogens, and this mutagenesis is of particular interest for viral pathogenesis and evolution. Here, we investigated the effect of NO on viral replication and mutation. Exogenous or endogenous NO had no apparent antiviral effect on influenza A virus and Sendai virus. The mutagenic potential of NO was analyzed with Sendai virus fused to a green fluorescent protein (GFP) gene (GFP-SeV). GFP-SeV was cultured in SW480 cells transfected with a vector expressing inducible NO synthase (iNOS). The mutation frequency of GFP-SeV was examined by measuring loss of GFP fluorescence of the viral plaques. GFP-SeV mutation frequency in iNOS-SW480 cells was much higher than that in parent SW480 cells and was reduced to the level of mutation frequency in the parent cells by treatment with an NO synthase (NOS) inhibitor. Immunocytochemistry showed generation of more 8-nitroguanosine in iNOS-SW480 cells than in SW480 cells without iNOS transfection. Authentic 8-nitroguanosine added exogenously to GFP-SeV-infected CV-1 cells increased the viral mutation frequency. Profiles of the GFP gene mutations induced by 8-nitroguanosine appeared to resemble those of mutations occurring in mouse lungs in vivo. A base substitution that was characteristic of both mutants (those induced by 8-nitroguanosine and those occurring in vivo) was a C-to-U transition. NO-dependent oxidative stress in iNOS-SW480 cells was also evident. Together, the results indicate unambiguously that NO has mutagenic potential for RNA viruses such as Sendai virus without affecting viral replication, possibly via 8-nitroguanosine formation and cellular oxidative stress.

Animals↗
PubMed1984

Viral infections of the nervous system.

Neurotropic viruses cause a number of important infectious syndromes including encephalitis, myelitis, meningitis, and radiculopathy. In this review, the biology of conventional and unconventional viruses is examined. The host immune response to viruses is discussed, and patterns of viral pathogenesis are explained. The clinical features, laboratory findings, management of important viral infections, such as herpes simplex encephalitis and epidemic encephalitis, are presented. Post-infection syndromes, such as the Guillain-Barré syndrome, and chronic viral infections, such as those causing progressive multifocal leukoencephalopathy and subacute sclerosing panencephalitis, are discussed. Current knowledge concerning the nature of unconventional virus-like agents of the spongiform encephalopathies, including kuru and Creutzfeldt-Jakob disease, is summarized. Finally, viral infections of immunocompromised patients and the possible role of viruses in the newly described acquired immunodeficiency syndrome (AIDS) are examined.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Relevance of studies of cellular receptors to the prevention and control of viral disease: memorandum from a WHO meeting.

This Memorandum describes recent scientific advances in the identification and characterization of cell receptors for viruses and their relevance to programmes for the prevention and control of viral diseases. These areas of anti-viral research provide an improved understanding of the mechanisms of viral pathogenesis and a rational basis for the development of anti-viral drugs, viral vaccines, and new diagnostic approaches and reagents. Advances in research to characterize the cellular receptors for human picornaviruses (including poliovirus, coxsackievirus and rhinovirus), influenza viruses, and reoviruses are reviewed.

Humans↗
PubMed2004

Immunomodulatory effects of the HIV-1 gp120 protein on antigen presenting cells: implications for AIDS pathogenesis.

Antigen presenting cell (APC) function is central to the development of an effective anti-viral immune response. Among APC, monocytes, macrophages and dendritic cells (DC) form the principal non-T cell compartment involved in in vivo HIV infection, and these cells play important and well-established roles in multiple aspects of viral pathogenesis. HIV infection may result in APC defects, which could ultimately contribute to the loss of CD4+ T cell responses observed early in HIV infection, when the CD4+ T cell number is still within the normal range. Extensive in vitro studies have demonstrated that the envelope glycoproteins of HIV-1 exert profound influences on various cell populations of the immune system, including hematopoietic progenitors, T and B lymphocytes, monocytes/ macrophages and DC, as well as on neuronal cells. The demonstration of the presence of envelope proteins both free in the circulation and bound to the surface of CD4+ cells suggests that gp120 interactions with non-infected cells can influence cellular functions in vivo, thus contributing to the immunopathogenesis of AIDS. This paper provides an overview of the present knowledge on gp120 binding, signal transduction triggering and interference with macrophage and DC functions and it highlights the importance of this interaction in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗