The Viral Chemokine MCK-2 of Murine Cytomegalovirus Promotes Infection as Part of a gH/gL/MCK-2 Complex

Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus. For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described. Knock-out of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex. Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion. We could additionally show that mutants lacking both, gO and MCK-2 are not able to produce infectious virus. Trans-complementation of these double mutants with either gO or MCK-2 showed that both proteins can promote infection of host cells, although through different entry pathways. MCK-2 has been extensively studied in vivo by others. It has been shown to be involved in attracting cells for virus dissemination and in regulating antiviral host responses. We now show that MCK-2, by forming a complex with gH, strongly promotes infection of macrophages in vitro and in vivo. Thus, MCK-2 may play a dual role in MCMV infection, as a chemokine regulating the host response and attracting specific target cells and as part of a glycoprotein complex promoting entry into cells crucial for virus dissemination.     

Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity

In most adult humans, hepatitis B is a self-limiting disease leading to life-long protective immunity, which is the consequence of a robust adaptive immune response occurring weeks after hepatitis B virus (HBV) infection. Notably, HBV-specific T cells can be detected shortly after infection, but the mechanisms underlying this early immune priming and its consequences for subsequent control of viral replication are poorly understood. Using primary human and mouse hepatocytes and mouse models of transgenic and adenoviral HBV expression, we show that HBV-expressing hepatocytes produce endoplasmic reticulum (ER)-associated endogenous antigenic lipids including lysophospholipids that are generated by HBV-induced secretory phospholipases and that lead to activation of natural killer T (NKT) cells. The absence of NKT cells or CD1d or a defect in ER-associated transfer of lipids onto CD1d results in diminished HBV-specific T and B cell responses and delayed viral control in mice. NKT cells may therefore contribute to control of HBV infection through sensing of HBV-induced modified self-lipids.     

Annexin II incorporated into influenza virus particles supports virus replication by converting plasminogen into plasmin

For influenza viruses to become infectious, the proteolytic cleavage of hemagglutinin (HA) is essential. This usually is mediated by trypsin-like proteases in the respiratory tract. The binding of plasminogen to influenza virus A/WSN/33 leads to the cleavage of HA, a feature determining its pathogenicity and neurotropism in mice. Here, we demonstrate that plasminogen also promotes the replication of other influenza virus strains. The inhibition of the conversion of plasminogen into plasmin blocked influenza virus replication. Evidence is provided that the activation of plasminogen is mediated by the host cellular protein annexin II, which is incorporated into the virus particles. Indeed, the inhibition of plasminogen binding to annexin II by using a competitive inhibitor inhibits plasminogen activation into plasmin. Collectively, these results indicate that the annexin II-mediated activation of plasminogen supports the replication of influenza viruses, which may contribute to their pathogenicity.     

Experimental evaluation of microarterial grafts in rats and rabbits: long-term histological studies.

This experimental study was done to compare the fate of microarterial grafts versus microvenous grafts. Based on morphological aspects, patency rates, and histological features, the arterial grafts gave better long-term results than the venous grafts--due mainly to an absence of subintimal fibrotic changes in the microarterial grafts.     

Activity and Distribution of Methane-Oxidizing Bacteria in Flooded Rice Soil Microcosms and in Rice Plants (Oryza sativa)

The activity and distribution of CH(inf4)-oxidizing bacteria (MOB) in flooded rice (Oryza sativa) soil microcosms was investigated. CH(inf4) oxidation was shown to occur in undisturbed microcosms by using (sup14)CH(inf4), and model calculations indicated that almost 90% of the oxidation measured had taken place at a depth where only roots could provide the O(inf2) necessary. Slurry from soil planted with rice had an apparent K(infm) for CH(inf4) of 4 (mu)M and a V(infmax) of 0.1 (mu)mol g (dry weight)(sup-1) h(sup-1). At a depth of 1 to 2 cm, there was no significant difference (P > 0.05) in numbers of MOB between soil from planted and nonplanted microcosms (mean, 7.7 x 10(sup5) g [fresh weight](sup-1)). Thus, the densely rooted soil at 1 to 2 cm deep did not represent rhizospheric soil with respect to the number of MOB. A significantly increased number of MOB was found only in soil immediately around the roots (1.2 x 10(sup6) g [fresh weight](sup-1)), corresponding to a layer of 0.1 to 0.2 mm. Plant-associated CH(inf4) oxidation was shown in a double chamber with carefully washed intact rice plants. Up to 90% of the CH(inf4) supplied to the root compartment was oxidized in the plants. CH(inf4) oxidation on isolated roots was higher and had a larger variability than that in soil slurries. Roots had an apparent K(infm) for CH(inf4) of 6 (mu)M and a V(infmax) of 5 (mu)mol g (dry weight)(sup-1) h(sup-1). The average number of MOB in homogenized roots was larger than on the rhizoplane and increased with plant age. MOB also were found in surface-sterilized roots and basal culms, indicating the ability of these bacteria to colonize the interior of roots and culms.