Complement protein C1q, the recognition molecule of the classical pathway, performs a diverse range of complement and non-complement functions. It can bind various ligands derived from self, non-self, and altered self and modulate the functions of immune and non-immune cells including dendritic cells and microglia. C1q involvement in the clearance of apoptotic cells and subsequent B cell tolerance is more established now. Recent evidence appears to suggest that C1q plays an important role in pregnancy where its deficiency and dysregulation can have adverse effects, leading to preeclampsia, missed abortion, miscarriage or spontaneous loss, and various infections. C1q is also produced locally in the central nervous system, and has a protective role against pathogens and possible inflammatory functions while interacting with aggregated proteins leading to neurodegenerative diseases. C1q role in synaptic pruning, and thus CNS development, its anti-cancer effects as an immune surveillance molecule, and possibly in aging are currently areas of extensive research.

The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.

Introns from the Epstein-Barr virus (EBV) BART RNAs produce up to 20 micro RNAs (miRNAs) but the spliced exons of the BART RNAs have also been investigated as possible mRNAs, with the potential to express the RPMS1 and A73 proteins. Recombinant RPMS1 and A73 proteins were expressed in Escherichia coli and used to make new monoclonal antibodies that reacted specifically with artificially expressed RPMS1 and A73. These antibodies did not detect endogenous expression of A73 and RPMS1 proteins in a panel of EBV-infected cell lines representing the different known types of EBV infection. BART RNA could not be detected on Northern blots of cytoplasmic poly(A) + RNA from the C666.1 NPC cell line and BART RNA was found to be mainly in the nucleus of C666.1 cells, arguing against an mRNA role for BART RNAs. In contrast, some early lytic cycle EBV mRNAs were found to be expressed in C666.1 cells. Artificially expressed A73 protein was known to be able to bind to the cellular RACK1 protein and has now also been shown to be able to regulate calcium flux, presumably via RACK1. Overall, the results support the conclusion that the miRNAs are functionally important products of BART transcription in the cell lines studied because the A73 and RPMS1 proteins could not be detected in natural EBV infections. However, the possibility remains that A73 and RPMS1 might be expressed in some situations because of the clear potential relevance of their biochemical functions. INTRODUCTIONThe BART RNAs are a heterogeneously spliced group of Epstein-Barr virus (EBV) RNAs transcribed rightward from position 138 352 to 160 531 on the EBV wild-type genetic map (Sadler & Raab-Traub, 1995; Smith et al., 2000;de Jesus et al., 2003). BART RNAs have been detected in peripheral blood of normal EBV carriers (Chen et al., 1999) and in all EBV-associated diseases that have been examined, including Burkitt's lymphoma (Tao et al., 1998), gastric carcinoma (Sugiura et al., 1996), salivary gland carcinomas , oral hairy leukoplakia (Webster-Cyriaque & Raab-Traub, 1998), nasal natural killer and T cell lymphomas (Chiang et al., 1996;van Gorp et al., 1996), Hodgkin's lymphoma (Deacon et al., 1993) and hepatocellular carcinomas (Sugawara et al., 1999). Most of the viral micro RNAs (miRNAs) that are expressed in EBV latent infections are derived from the BART RNAs (Cai et al., 2006; Griffiths-Jones et al., 2006;Grundhoff et al., 2006;Pfeffer et al., 2004). The BART miRNAs are thought to be derived mainly from introns prior to splicing of the BART primary transcripts (Edwards et al., 2008). Few functional targets have yet been identified for the EBV miRNAs but there is evidence that miR BART2 can regulate the EBV DNA polymerase gene (Barth et al., 2008) and miR BART 1-5p and 17-5p can regulate EBV LMP1 (Lo et al., 2007).The BART RNAs (also known as complementary strand transcripts or BARF0 RNAs) were originally identified by analysis of cDNA libraries established from the nudemouse-passaged nasopharyngeal carcinoma (NPC) cell line C15 (Gilligan et al., 1990;Hit...

Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SP-D against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection.