Furthermore, infected macrophages appear to contribute to dementia and neural dysfunction in infected individuals. However, unlike CD4 + T cells, macrophages express relatively low levels of CD4 thereby complicating efficient viral entry. Additional attachment factors, including carbohydrate receptors, have been proposed to facilitate infection of macrophages. On their surface, macrophages express a number of C-type lectins, including the macrophage mannose receptor and DEC-205. Although both the MMR and DEC-205 can capture HIV-1 through recognition of mannose-associated glycans on the viral envelope protein, binding to these BAY 73-4506 receptors results primarily in non-productive infection or internalization of the virus for antigen presentation. In addition to the C-type lectins, macrophages also express a number of Sialic acid-binding immunoglobulin-like lectins. In humans, the Siglec family is comprised of a total of 14 different genes that specifically recognize terminal sialic acids associated with both N- and Olinked glycosylations. They are expressed mainly on lymphoid and myeloid BKM120 lineage cells where they promote cell-to-cell adhesion through binding to cell surface-associated sialic acids. Siglecs are also known to recognize heavily glycosylated mucins and mucin-like domains. Like many enveloped retroviruses, the envelope protein of HIV- 1 is heavily glycosylated. The crystal structure of the viral envelope protein revealed the molecular details of the CD4 binding site on gp120. Mutations in gp120 that remove N-linked glycan sites on both HIV and SIV have resulted in viruses that are more sensitive to neutralization, suggesting a role of the viral glycan in shielding against host immune detection. However, some of the mutants, especially those with multiple glycan mutations, also displayed much lower viral infectivity and syncytia-forming ability compared to the wild-type viruses, indicating a potential involvement of these glycans in viral entry. The best studied example involving sialic acid in viral entry is the Orthomyxoviridae family of influenza viruses, which use hemagglutinin as the attachment receptor to bind to cell surface sialic acids. HIV and many other enveloped viruses do not encode hemagglutinin for sialic acid binding. Rather, these viruses can have N-terminal sialic acid bound to envelope-associated proteins, like gp120 on HIV-1. Interestingly, it has been shown that removal of cell surface sialic acids via neuraminidase treatment enhances HIV infection. Recently, evidence suggests that sialoadhesin on a transfected monocytic cell line can interact with HIV-1. In addition, Siglec-1 expression is up-regulated on certain populations of monocytes upon HIV-1 infection. It is not clear, however, whether Siglec-1 recognizes heavily glycosylated viral envelope proteins, such as HIV-1 gp120, and if the increased expression of Siglec-1 would facilitate viral attachment and entry.