PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 10854657

Persisting viruses and autoimmunity.

M Paroli·E Schiaffella·F Di Rosa·V Barnaba
View original source ↗Export metadata ↓

Abstract

Viral infections can be responsible for the onset and sustaining of autoimmune processes. We discuss how chronic inflammation associated with viral persistence is the prerequisite for initiation of a multi-step process leading to autoimmunity. Firstly, chronic inflammation may favor the priming of autoreactive T cells that have escaped thymic selection and are specific for self-mimicking viral peptides in the periphery. In addition, viral persistence and inflammation can act synergistically to induce and sustain autoimmunity either unveiling cryptic self-epitopes, or favoring determinant spreading, or activating dendritic cells, or promoting constant priming of new autoreactive T cells, or contributing to the efficient generation of effector cells, or, finally, restimulating memory T lymphocytes.

Explore related subjects

Antigens, ViralDemyelinating Autoimmune Diseases, CNSHumansT-LymphocytesVirus DiseasesJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M Paroli, E Schiaffella, F Di Rosa, V Barnaba. 2000-07-24. Persisting viruses and autoimmunity.. https://doi.org/10.1016/s0165-5728(00)00228-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Avian-virus-like receptor specificity of the hemagglutinin impedes influenza virus replication in cultures of human airway epithelium.

A non-optimal receptor-binding specificity of avian influenza viruses is believed to hamper their replication in humans; however, the magnitude of this restriction remains undefined. Here we generated recombinant viruses, R1 and R2, that differed solely by two amino acids in the receptor-binding site of their hemagglutinin (HA). R1 harbored the original HA of the pandemic human virus A/Hong Kong/1/68 (H3N2), whereas R2 was the L226Q/S228G HA mutant with avian-virus-like receptor specificity. In differentiated cultures of human tracheo-bronchial epithelial cells, R1 preferentially infected non-ciliated cells, whereas R2 predominantly infected ciliated cells indicating that cell tropism was determined by the viral receptor specificity. In the course of multi-cycle replication in these cultures, R2 spread less efficiently and grew to 2-10-fold lower titers than did R1. These results for the first time estimate the level of receptor-dependent restriction of avian influenza viruses in human airway epithelium. They support a theory that alteration of the receptor specificity of an avian virus could facilitate its human-to-human transmission.

Antigens, Viral↗
PubMed2007

Assembly of hepatitis delta virus: particle characterization, including the ability to infect primary human hepatocytes.

Efficient assembly of hepatitis delta virus (HDV) was achieved by cotransfection of Huh7 cells with two plasmids: one to provide expression of the large, middle, and small envelope proteins of hepatitis B virus (HBV), the natural helper of HDV, and another to initiate replication of the HDV RNA genome. HDV released into the media was assayed for HDV RNA and HBV envelope proteins and characterized by rate-zonal sedimentation, immunoaffinity purification, electron microscopy, and the ability to infect primary human hepatocytes. Among the novel findings were that (i) immunostaining for delta antigen 6 days after infection with 300 genome equivalents (GE) per cell showed only 1% of cells as infected, but this was increased to 16% when 5% polyethylene glycol was present during infection; (ii) uninfected cells did not differ from infected cells in terms of albumin accumulation or the presence of E-cadherin at cell junctions; and (iii) sensitive quantitative real-time PCR assays detected HDV replication even when the multiplicity of infection was 0.2 GE/cell. In the future, this HDV assembly and infection system can be further developed to better understand the mechanisms shared by HBV and HDV for attachment and entry into host cells.

Antigens, Viral↗
PubMed2007

Human herpesvirus 8-encoded proteins with potential roles in virus-associated neoplasia.

Human herpesvirus 8 (HHV-8) is a gamma-2 herpesvirus, related genetically to simian herpesvirus saimiri (HVS), the prototype virus of this subgroup of the gammaherpesvirus subfamily. HHV-8 DNA is present in all forms of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), and in most forms of multicentric Castleman's disease (MCD), especially in HIV infected individuals. Of relevance to attempts to explain the molecular basis of HHV-8 associated neoplasia, are the unique genes specified by this virus, in particular angiogenic cytokines viral interleukin-6 (vIL-6) and viral CC-class chemokines (vCCL-1, vCCL-2, vCCL-3), mitogenic signaling membrane proteins variable ITAM-containing protein (VIP) and latency associated membrane protein (LAMP), pro-survival latently-expressed viral interferon regulatory factor (vIRF3), and the kaposin family of proteins that promote cell growth and cytokine production. Also of relevance are the angiogenic and cytokine-inducing viral G protein-coupled receptor (vGPCR), pro-proliferative and pro-survival latency proteins viral FLICE inhibitory protein (vFLIP) and latency-associated nuclear antigen (LANA), and G1-S phase cell-cycle promoter viral cyclin (v-cyclin), proteins specified also by other gamma-2 herpesviruses. The enormous progress on the characterization of the properties and biological activities of these proteins over the last ten years has provided insight into the potential mechanisms of HHV-8-induced neoplasia. Present data suggest that there operates a combination of cell transformation mediated by latently expressed proteins that promote cell proliferation and survival coupled with paracrine signaling functions mediated by either the viral cytokines or viral receptor-induced secreted cellular proteins. This review discusses the properties of the viral proteins believed to contribute to viral neoplasia via these mechanisms.

Antigens, Viral↗