The ability of HIV-1 to use dendritic cells (DCs) for transport and to transfer virus to activated T cells in the lymph node may be crucial in early HIV-1 pathogenesis. We have characterized primary DCs for the receptors involved in viral envelope attachment and observed that C-type lectin receptor (CLR) binding was predominant in skin DCs, whereas binding to emigrating and tonsil DCs was CD4-dependent. No one CLR was solely responsible for envelope binding on all skin DC subsets. DC-SIGN (DC-specific ICAM-3-grabbing nonintegrin) was only expressed by CD14(+)CDla(lo) dermal DCs. The mannose receptor was expressed by CD1a(hi) and CD14(+)CDla(lo) dermal DCs, and langerin was expressed by Langerhans cells. The diversity of CLRs able to bind HIV-1 in skin DCs may reflect their ability to bind a range of microbial glycoproteins.

Hepatitis C virus (HCV) is an enveloped, positive-stranded RNA virus classified in the family Flaviviridae. Infection is often associated with chronic disease, sometimes resulting in hepatitis, cirrhosis, and hepatocellular carcinoma. Although chronic infection occurs in up to 70% of individuals, the mechanisms leading to viral persistence have not been defined. The principal site of replication is thought to be the liver, although several laboratories have suggested that HCV may infect a wider range of cell types, including monocytes/macrophages and B cells (28,33,44).HCV encodes two putative envelope glycoproteins, E1 and E2, which are believed to be type I integral transmembrane proteins with C-terminal hydrophobic anchor domains. In vitro expression studies have shown that both glycoproteins associate to form heterodimers, which accumulate in the endoplasmic reticulum, the proposed site for HCV assembly and budding (reviewed in reference 53). Being an enveloped virus, HCV likely interacts with specific cell surface receptors that either induce conformational changes in the E1 and E2 glycoproteins, resulting in fusion between the viral and cellular membranes, or mediate internalization of virus particles to endosomes, where the acidic environment triggers membrane fusion-inducing conformational changes. The E2 glycoprotein is thought to be responsible for initiating virus attachment (29,54,67,71), and we have hypothesized that the E1 glycoprotein contains the fusion peptide responsible for mediating fusion of the virus and cell membranes (31).The lack of in vitro systems for HCV propagation has hampered biological and physiochemical studies of the virion and its mechanism of cell entry, so that the cellular receptors remain unknown. Difficulties encountered in purifying sufficient quantities of HCV from plasma have limited studies with native virus. In addition, HCV purified from plasma has been reported to exist in association with immune complexes and plasma lipoproteins (2, 6, 57). The association of the virus with lipoproteins has led to the suggestion that HCV may use the low-density lipoprotein receptor to gain entry into cells (3,71).In the absence of native HCV particles, virus-like particles expressed in insect cell systems (11,15,63,67) and truncated versions of the E2 glycoprotein have been used as mimics to study virus-cell interactions (29,54,58). Truncated E2 binds specifically to human cells and was used to identify CD81 as a putative receptor for some HCV strains (54). Recent reports suggest antigenic differences between the truncated form of E2 and that present on virus-like particles for reactivity with E2-specific monoclonal antibodies and CD81 (15,63,67). Since CD81 is expressed on the majority of cell types, it is unlikely to be the sole determinant of viral tropism, and additional cell surface molecules may be required for HCV entry into a target cell (45).While virus receptors typically play important roles in defining virus tropism, other cell surface molecules can significantly enhanc...

The C-type lectins DC-SIGN and DC-SIGNR [collectively referred to as DC-SIGN(R)] bind and transmit human immunodeficiency virus (HIV) and simian immunodeficiency virus to T cells via the viral envelope glycoprotein (Env).Other viruses containing heavily glycosylated glycoproteins (GPs) fail to interact with DC-SIGN(R), suggesting some degree of specificity in this interaction. We show here that DC-SIGN(R) selectively interact with HIV Env and Ebola virus GPs containing more high-mannose than complex carbohydrate structures. Modulation of N-glycans on Env or GP through production of viruses in different primary cells or in the presence of the mannosidase I inhibitor deoxymannojirimycin dramatically affected DC-SIGN(R) infectivity enhancement. Further, murine leukemia virus, which typically does not interact efficiently with DC-SIGN(R), could do so when produced in the presence of deoxymannojirimycin. We predict that other viruses containing GPs with a large proportion of high-mannose N-glycans will efficiently interact with DC-SIGN(R), whereas those with solely complex N-glycans will not. Thus, the virus-producing cell type is an important factor in dictating both N-glycan status and virus interactions with DC-SIGN(R), which may impact virus tropism and transmissibility in vivo.

Symbiotic nitrogen recycling enables animals to thrive on nitrogen-poor diets and environments. It traditionally refers to the utilization of animal waste nitrogen by symbiotic micro-organisms to synthesize essential amino acids (EAAs), which are translocated back to the animal host. We applied metabolic modelling and complementary metabolite profiling to investigate nitrogen recycling in the symbiosis between the pea aphid and the intracellular bacterium Buchnera, which synthesizes EAAs. The results differ from traditional notions of nitrogen recycling in two important respects. First, aphid waste ammonia is recycled predominantly by the host cell (bacteriocyte) and not Buchnera. Host cell recycling is mediated by shared biosynthetic pathways for four EAAs, in which aphid transaminases incorporate ammonia-derived nitrogen into carbon skeletons synthesized by Buchnera to generate EAAs. Second, the ammonia substrate for nitrogen recycling is derived from bacteriocyte metabolism, such that the symbiosis is not a sink for nitrogenous waste from other aphid organs. Host cell-mediated nitrogen recycling may be general among insect symbioses with shared EAA biosynthetic pathways generated by the loss of symbiont genes mediating terminal reactions in EAA synthesis.

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