Viruses are parasites. They depend on the biochemical infrastructure
of host cells to grow. A key element of the infrastructure provided
by the host cell is its metabolic machinery, which viruses rely upon
to provide the energy and building blocks necessary for their
replication. The way in which viruses interact with host cell
metabolism remains, however, poorly understood. The authors
have used an advanced measurement technique, liquid chromatography-
mass spectrometry, to quantitate directly the levels of a large
number of metabolic compounds (energy molecules and biochemical
building blocks) during cytomegalovirus infection of cultured
human cells. They find that viral infection leads to dramatic increases
in the levels of many metabolites and that these increases
substantially exceed those associated with normal transitions of
cells between resting and growing states. In several cases, enhanced
metabolite levels induced by the virus coincide with an apparent
increase in host cell production of the machinery (enzymes) involved
in making those metabolites.
Entering the host cell
Endocytosis and virus entry
Enterovirus 71-induced autophagy detected in vitro and in vivo promotes viral replication. 2009
J Med Virol. 2009, 81(7):1241-52.
Huang SC, Chang CL, Wang PS, Tsai Y, Liu HS.
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Enterovirus 71 (EV71) is an important pathogen causing death in children under 5 years old worldwide. However, the underlying pathogenesis remains unclear. This study reveals that EV71 infection in rhabdomyosarcoma (RD) and neuroblastoma (SK-N-SH) cells stimulated the autophagic process, which was demonstrated by an increase of punctate GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3), the level of autophagosome-bound LC3-II protein and double-membrane autophagosome formation. EV71-induced autophagy benefited EV71 replication, which was confirmed by the autophagic inducer rapamycin and the inhibitor 3-methyladenine. Signaling pathway investigation revealed that the decreased expression of phosphorylated mTOR and phosphorylated p70S6K is involved in EV71-induced autophagy in a cell-specific manner. The expression of phosphorylated extracellular signal-regulated kinase (Erk) was suppressed consistently in EV71-infected cells. However it did not participate in the autophagic response of the cell. Other signaling pathway molecules, such as Erk, PI3K/Akt, Bcl-2, BNIP3, and Beclin-1 were not affected by infection with EV71. Electron microscopy showed co-localization of autophagosome-like vesicles with either EV71-VP1 or LC3 protein in neurons of the cervical spinal cord in ICR mice infected with EV71. In conclusion, EV71 infection triggered autophagic flux and induced autophagosome formation both in vitro and in vivo. Autophagy induced by EV71 is beneficial for viral replication. Understanding the role of autophagy induced by EV71 in vitro and the formation of autophagosome-like vesicle in vivo provide new insights into the pathogenesis of EV71 infection. Copyright 2009 Wiley-Liss, Inc.
Rev Med Virol. 2000 Sep-Oct;10(5):305-19.
The novel receptors that mediate the entry of herpes simplex viruses and animal alphaherpesviruses into cells. 2000
Campadelli-Fiume G, Cocchi F, Menotti L, Lopez M.
Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, Via San Giacomo 12, 40126 Bologna, Italy. firstname.lastname@example.org
An extended array of cell surface molecules serve as receptors for HSV entry into cells. In addition to the heparan sulphate glycosaminoglycans, which mediate the attachment of virion to cells, HSV requires an entry receptor. The repertoire of entry receptors into human cells includes molecules from three structurally unrelated molecular families. They are (i) HveA (herpesvirus entry mediator A), (ii) members of the nectin family, (iii) 3-O-sulphated heparan sulphate. The molecules have different attributes and play potentially different roles in HSV infection and spread to human tissues. All the human entry receptors interact physically with the virion envelope glycoprotein D (gD). (i) HveA is a member of the TNF-receptor family. It mediates entry of a restricted range of HSV strains. Its expression is restricted to few lineages (e.g. T-lymphocytes). (ii) The human nectin1alpha (HIgR), nectin1delta (PRR1-HveC), and the nectin2alpha (PRR2alpha-HveB) and nectin2delta (PRR2delta) belong to the immunoglobulin superfamily. They are homologues of the poliovirus receptor (CD155), with which they share the overall structure of the ectodomain. The human nectin1alpha-delta are broadly expressed in cell lines of different lineages, are expressed in human tissue targets of HSV infection, serve as receptors for all HSV-1 and HSV-2 strains tested and mediate entry not only of free virions, but also cell-to-cell spread of virus. (iii) The 3-O-sulphated heparan sulphate is expressed in some selected human cell lines (e.g. endothelial and mast cells) and human tissues, and mediates entry of HSV-1, but not HSV-2. The human nectin2alpha and nectin2delta serve as receptors for a narrow range of viruses. A characteristic of the human nectin1alpha-delta is the promiscuous species non-specific receptor activity towards the animal alphaherpesviruses, pseudorabies virus (PrV) and bovine herpesvirus 1 (BHV-1). By contrast with the human nectin1delta, its murine homologue (mNectin1delta) does not bind gD at detectable level, yet it mediates entry of HSV, as well as of PrV and BHV-1. This provides the first example of a mediator of HSV entry independent of a detectable interaction with gD. Copyright 2000 John Wiley & Sons, Ltd.
J Virol. 2009 Jul;83(14):6978-86. Epub 2009 May 6.
Comparison of the pseudorabies virus Us9 protein with homologs from other veterinary and human alphaherpesviruses.
Lyman MG, Kemp CD, Taylor MP, Enquist LW.
Department of Molecular Biology, 314 Schultz Laboratory, Princeton, NJ 08544, USA.
Pseudorabies virus (PRV) Us9 is a small, tail-anchored (TA) membrane protein that is essential for axonal sorting of viral structural proteins and is highly conserved among other members of the alphaherpesvirus subfamily. We cloned the Us9 homologs from two human pathogens, varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1), as well as two veterinary pathogens, equine herpesvirus type 1 (EHV-1) and bovine herpesvirus type 1 (BHV-1), and fused them to enhanced green fluorescent protein to examine their subcellular localization and membrane topology. Akin to PRV Us9, all of the Us9 homologs localized to the trans-Golgi network and had a type II membrane topology (typical of TA proteins). Furthermore, we examined whether any of the Us9 homologs could compensate for the loss of PRV Us9 in anterograde, neuron-to-cell spread of infection in a compartmented chamber system. EHV-1 and BHV-1 Us9 were able to fully compensate for the loss of PRV Us9, whereas VZV and HSV-1 Us9 proteins were unable to functionally replace PRV Us9 when they were expressed in a PRV background.
Protecting the host cell
Source: Public Library of Science
Date: May 18, 2007
Microbes and More, Virology, Bacteria, Biology, Computational Biology,
Insignia: A New Way To Identify Viruses And Bacteria
Science Daily - Now that the genome sequences of hundreds of bacteria and
viruses are known, we can design tests that will rapidly detect the presence
of these species based solely on their DNA. These tests can detect a
pathogen in a complex mixture of organic material by recognizing short,
distinguishing sequences--called DNA signatures--that occur in the pathogen
and not in any other species.
Adam Phillippy and colleagues from the University of Maryland, USA, have
developed a computer program that can identify these signatures with a
higher degree of accuracy than ever before. They describe this new
computational system, called Insignia, and the results of its successful
application on 46 Vibrio cholerae strains this week in the Open Access
journal PLoS Computational Biology.
Competition for Iron
Viral infection and iron metabolism 2008
All virus with their own Ribonucleotide Reductase compete for iron with the host
Virus persistance and Laboratory tests sensitivity
Hcv infettivo persiste dopo risposta virologica
L'Hcv che persiste nonostante un'apparente risposta virologica prolungata puÃÂ² mantenere la propria infettivitÃÂ in vitro. Dato che l'identificazione di un'infezione da Hcv occulta si rende possibile solo con l'impiego di test di ricerca di sensibilitÃÂ di gran lunga maggiore rispetto a quelli disponibili in commercio, non sorprende che bassi livelli di Hcv RNA sfuggano di frequente al rilevamento nella pratica clinica, dando luogo a dati conflittuali su persistenza ed infettivitÃÂ dell'Hcv a livelli tracciabili. In generale, l'esistenza di infezioni occulte da Hcv non dovrebbe essere una situazione inattesa, considerato che altre infezioni da virus non citopatici tendono di frequente a divenire croniche, in un quadro in cui il sistema immunitario dell'ospite svolge un ruolo nella limitazione della diffusione del virus e nella risoluzione piÃÂ¹ o meno efficace dell'infiammazione che esso induce. (