Mæði-visnuveira og HIV: Margt er líkt með skyldum

Maedi-visna virus (MVV) is a lentivirus of sheep causing inflammation in many organs, primarily the lungs and CNS. HIV and SIV also belong to the lentivirus genus of retroviruses. MVV and HIV have many features in common, including genome organization, mode of virus replication, virus-host interaction and latency. Both viruses infect cells of the monocyte/macrophage lineage, but the main difference in cell tropism is that, whereas HIV infects T lymphocytes, MVV does not. Here, the molecular biology, cell tropism and pathogenesis of MVV are reviewed and some of the similarities as well as the dissimilarities between MVV and HIV are discussed.Mæði-visnuveira sýkir kindur og veldur aðallega lungnabólgu (mæði) og heilabólgu (visnu). Veiran er lentiveira og er náskyld alnæmisveirunni HIV. Veirurnar eiga margt sameiginlegt, svo sem skipulag erfðaefnis, virkni og gerð veirupróteina, fjölgunarferli, viðbrögð hýsils við sýkingu og dvalasýkingu, sem hýsillinn losnar aldrei við. Báðar veirur sýkja frumur ónæmiskerfisins; mæði-visnuveira sýkir átfrumur, en HIV sýkir bæði átfrumur og T-eitilfrumur. Í þessari yfirlitsgrein verða ýmis líkindi með þessum veirum reifuð.Peer Reviewe

Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs)

Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties. Using sheep blood monocytes and in vitro-derived macrophages, we found that A3Z1 expression is associated with lower viral replication in this cellular type. A3Z1 transcripts may also contain spliced variants (A3Z1Tr) lacking the cytidine deaminase motif. A3Z1 exogenous expression in fully permissive fibroblast-like cells restricted SRLVs infection while A3Z1Tr allowed infection. A3Z1Tr was induced after SRLVs infection or stimulation of blood-derived macrophages with interferon gamma (IFN-γ). Interaction between truncated isoform and native A3Z1 protein was detected as well as incorporation of both proteins into virions. A3Z1 and A3Z1Tr interacted with SRLVs Vif, but this interaction was not associated with degradative properties. Similar A3Z1 truncated isoforms were also present in human and monkey cells suggesting a conserved alternative splicing regulation in primates. A3Z1-mediated retroviral restriction could be constrained by different means, including gene expression and specific alternative splicing regulation, leading to truncated protein isoforms lacking a cytidine-deaminase motifWe sincerely acknowledge Sandra Hervás-Stubbs from CIMA for her fruitful help. We also acknowledge Greg Towers, University College London for plasmids and protocols. Funded by CICYT (AGL2010-22341-C04-01) and Navarra’s Government (IIQ010449.RI1, IIQ14064.RI1 and PI042-LENTIMOL). Ramsés Reina was supported by the Spanish Ministry of Science and Innovation “Ramón y Cajal” contract. We acknowledge support of the publication fee by the Public University of Navarra and CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

Nokkrir sambærilegir þættir í visnu og eyðni

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)It is clear that in addition to the relationship of visna virus and HIV and similar characteristics of their behavior in vitro, the host-virus interactions in infections with these viruses show several interesting parallels, such as target cells in the blood, mechanism of virus spread within the body and to some extent the target organs of infection. Although immunodeficiency is not a feature of visna virus infection, the pathological changes show some resemblance especially to those found in early stages of infection with HIV. The spectrum of target cells in the CNS in both infections is apparently similar. As there is increasing evidence that the nervous system is one of the primary target organs of infection with HIV, visna of sheep offers a promising possibility as a model for trials aimed at preventing or treating AIDS.Einn þeirra sjúkdóma, sem hugmynd Björns Sigurðssonar um sérstakan flokk smitsjúkdóma, hæggenga smitsjúkdóma (1), byggðist á, var visna. En visna er meningoencephalomyelitis í sauðfé og ein af hinum svonefndu Karakúlpestum. Orsökin reyndist vera retróveira og tókst að rækta hana 1957 (2). Visnuveiran er nú flokkuð ásamt ýmsum dýraveirum og eyðniveiru í undirflokk retróveira, sem nefnist lentiveirur (af lentus (lat.) = hægur). Það er mjög við hæfi að þessi flokkur veira skuli kenndur við hugmynd Björns enda visnuveiran sú fyrsta í þessum flokki, sem tókst að rækta. Lentiveirusýking í sauðfé var upprætt hérlendis fyrir aldarfjórðungi (3) en rannsóknum hefur verið haldið áfram, enda ósvarað mörgum ögrandi spurningum er varða bæði veiruna og víxlverkanir hýsils og veiru. Að auki teljum við að visna geti verið gagnlegt dýralíkan fyrir heila- og mænusigg (MS), vegna þess að sjúkdómurinn er að jafnaði langdreginn og stundum með endurteknum hviðum líkt og í MS og ekki síst að stundum sjást blettir (primary demyelination) sem líkjast mjög þeim sem taldir eru einkennandi fyrir vefjaskemmdir í MS (4). Uppá síðkastið hefur áhuginn beinst meira að því sem visna á sameiginlegt með eyðni, þareð veirurnar sem valda þessum sjúkdómum eru skyldar og hafa ýmsa sambærilega eiginleika bæði í rækt (in vitro) og í hýsli (in vivo). Ýmsum þáttum í viðbrögðum hýsils við eyðnisýkingu svipar til þess sem sést í visnu

The effect of maternal immunity on the equine gammaherpesvirus type 2 and 5 viral load and antibody response

Two types of gammaherpesviruses (γEHV) are known to infect horses, EHV-2 and EHV-5. Foals become infected early in life, probably via the upper respiratory tract, despite maternal antibodies. In this study, we analyzed samples from a herd of mares and their foals. The foals were followed from birth to 22 months of age and the dams during the first 6 months postpartum. Blood and nasal swab samples were taken regularly for evaluation of antibody responses, virus isolation and viral load by qPCR. EHV-2 was isolated on day 5, and EHV-5 on day 12, earlier than previously reported. γEHV specific antibodies were not detectable in serum of foals before colostrum intake but peaked a few days after colostrum. Overall, EHV-2 viral load peaked in nasal swab at three to four months of age, paralleled with decline in maternal antibodies, but EHV-5 viral load did not peak until month 12. Maternal antibodies had a notable effect on the viral load and induction of endogenous antibody production. Foals were grouped in two groups depending on the mare's γEHV specific total IgG levels in serum at birth, group-high and group-low. Group-high had higher levels of maternal γEHV specific total IgG and IgG4/7 for the first 3 months, but when the endogenous production had superseded maternal antibodies, group-low was higher. The maternal antibodies had an effect on the γEHV viral load. Group-low peaked in EHV-2 viral load one month earlier than group-high. These effects were more evident for EHV-5, as there were seven months between the viral load peaks for the groups. The study provides information on how maternal antibody transfer affects γEHV shedding and antibody production in offspring. It also extends our knowledge on the occurrence of EHV-2 and EHV-5 infection in foals during the first two years of life

Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue.

Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and 1 axillary metastatic growth) and 7 non-pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation. Fractions used were cytosol, mitochondria and microsomes. A comparison of two methods for detecting HK activity was made, yielding different results regarding HK II and HK III. A method based on the ability of NADPH to fluoresce in UV gave a constant pattern of HK isoenzymes. In non-pathological breast tissue, only HK I was seen, i.e. in the cytosol and the microsomal fractions. HK I was also seen in all fractions of the cancers, but another more anodal band of HK I, as well as HK II and HK III, consistently appeared in the cytosol fractions. The more commonly used staining technique with tetrazolium dye revealed HK II in 45% and HK III in 50% of the samples. The pattern of HK isoenzymes in the cancers was the same irrespective of estrogen and progesterone cytosolic receptor contents and the histology of the tumors. The fluorescence method is, therefore, much more sensitive than the tetrazolium technique for detecting HK activity after electrophoresis and could explain difference in results obtained by various laboratories

Catabolite repressive effects of 5-thio-D-glucose on Saccharomyces cerevisiae.

The effect of the glucose analogue 5-thio-D-glucose (5TG) on the yeast Saccharomyces cerevisiae was studied. Derepression of mitochondrial respiratory chain cytochromes, alcohol dehydrogenase (isoenzyme II), NADH dehydrogenase and maltase was inhibited by 0.5-2 mM-5TG. Growth rate was only slightly affected. Ethanol was efficiently produced with 2 mM-5TG in medium initially containing 0.25% glucose. Mutants resistant to the growth inhibitory effects of 5TG on glycerol medium showed resistance to the catabolite repressing effects of glucose. Other mutants, known to be catabolite repression resistant, showed resistance to 5TG. The analogue seems to inhibit derepression of glucose repressible enzymes with greater potency than glucose itself.Science Fund of Icelan

Comparison of sensitivity of Campy-Cefex dilution method and PCR in detecting Campylobacter in broilers

The aim of the study was to compare the sensitivity of a Campy-Cefex dilution method and PCR for detecting Campylobacter in broilers and to see if any traces of the bacteria were to be found by these methods during winter when the bacteria is not detectable by conventional microbiological methods. The results of our studies done in 2004 and 2005 were compared with data from 2001-2003 soon after a national surveillance of Campylobacter spp. in broilers was initiated. Faecal samples from 607 broiler flocks were pooled, 10 samples per pool, and diluted in saline for the Campy-Cefex direct plating dilution method and PCR. The PCR amplification was performed in a Peltier Thermal Cycler and the primers used were C412F and C1288R. A total of 742 pooled caecal samples were collected at slaughter. Samples from each pool of 40 caeca were diluted in saline for the Campy-Cefex direct plating dilution method. The PCR method proved to be more sensitive than the Campy-Cefex method but still did not detect any traces of Campylobacter during winter. A comparison of the results from 2001-2003 with the results from 2004-2005 indicates that the percentage of positive flocks had diminished. The study underlines the importance of using sensitive methods for detecting Campylobacter spp. in order to minimize the risk of human exposure. The finding that the sensitive PCR method was not able to detect Campylobacter during winter suggests that the seasonal pattern of campylobacteriosis is due to a new vector in the spring which carries the bacterium.Samanburður á næmi tveggja aðferða við greiningu á Campylobacter í kjúklingum, Campy-Cefex ræktunaraðferðar með raðþynningum og PCR aðferðar. Tilgangur rannsóknarinnar var að bera saman næmi tveggja aðferða við greiningu Campylobacter, Campy-Cefex ræktunaraðferðar með raðþynningum og PCR aðferðar. Þessar aðferðir voru notaðar við greiningu á bakteríunni úr kjúklingasýnum yfir vetur þegar lítið smit greinist með hefðbundnum ræktunaraðferðum. Niðurstöður rannsóknarinnar sem stóð yfir frá árinu 2004 til ársins 2005 eru bornar saman við upplýsingar frá árinu 2000 þegar farið var út í fyrirbyggjandi aðgerðir gegn Campylobacter smiti í kjúklingaeldi. Ræktað var úr 607 safnsýnum frá kjúklingum í eldi, 10 saursýni saman í sýni. Gerð var þynning á sýnunum í saltvatni og þeim sáð í raðþynningum út á skálar með Campy-Cefex agar. Sömu sýni voru mögnuð upp með C412F og C1288R vísum í „Peltier Thermal Cycler“ PCR tæki. Ræktað var úr 742 safnsýnum frá kjúklingum úr slátrun, 40 botnlangasýni saman. Sýnin voru raðþynnt í saltvatni og þeim sáð út á skálar með Campy-Cefex agar. PCR aðferðin reyndist næmari en Campy-Cefex aðferðin en hún greindi þó ekki nein merki um Campylobacter í kjúklingasýnum yfir vetrarmánuðina. Samanburður niðurstaðna við stöðuna í kjúklingaeldi árin 2001-2003 bendir til þess að hlutfall Campylobacter jákvæðra kjúklingahópa hefur minnkað á tímabilinu. Niðurstöður rannsóknarinnar undirstrika mikilvægi þess að nota næmar aðferðir við greiningu á Campylobacter til að lágmarka hættu á smiti í fólk. PCR aðferðin greindi ekki Campylobacter að vetri til og bendi það til þess að hin ársbundna sveifla í Campylobacter eigi rætur sínar að rekja til nýsmits að vori

Duplicated sequence motif in the long terminal repeat of maedi-visna virus extends cell tropism and is associated with neurovirulence

Maedi-visna virus (MW) is a lentivirus of sheep causing chronic inflammatory disease of the lungs (maedi) and the nervous system (visna). We have previously shown that a duplicated sequence in the long terminal repeat (LTR) of MVV is a determinant of cell tropism. Here, we demonstrate that deletion of a CAAAT sequence from either one of the repeats resulted in poor virus growth in sheep choroid plexus cells. A duplication in the LTR encompassing the CAAAT sequence was found in four neurological field cases that were sequenced, but no duplication was present in the LTRs from seven maedi cases; one maedi isolate was mixed. These results indicate that the duplication in the LTR is associated with neurovirulence.This work was supported by grants from the Icelandic Research Fund, the University of Iceland Research Fund, and the Icelandic Research Fund for Graduate Students

Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity

HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL) complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac]) and non-primate (FIV, BIV, and MVV) viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA), for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity

Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity.

HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL) complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac]) and non-primate (FIV, BIV, and MVV) viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA), for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity