Simian Immunodeficiency Virus Interactions with Macaque Dendritic Cells

Abstract

This chapter summarizes advances in the following areas: (1) dendritic cell (DC)-mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in innate and adaptive immunity against SIV, and (3) approaches to harness DC function to induce anti-SIV responses. The nonhuman primate (NHP) model of human immunodeficiency virus (HIV) infection in rhesus macaques and other Asian NHP species is highly relevant to advance the understanding of virus–host interactions critical for transmission and disease pathogenesis. HIV infection is associated with changes in frequency, phenotype, and function of the two principal subsets of DCs, myeloid DCs and plasmacytoid DCs. DC biology during pathogenic SIV infection is strikingly similar to that observed in HIV-infected patients. The NHP models provide an opportunity to dissect the requirements for DC-driven SIV infection and to understand how SIV distorts the DC system to its advantage. Furthermore, the SIV model of mucosal transmission enables the study of the earliest events of infection at the portal of entry that cannot be studied in humans, and, importantly, the involvement of DCs. Nonpathogenic infection in African NHP hosts allows investigations into the role of DCs in disease control. Understanding how DCs are altered during SIV infection is critical to the design of therapeutic and preventative strategies against HIV.

Rhadinovirus Host Entry by Co-operative Infection

“…Myeloid cells have roles in host colonization by several lymphotropic viruses [ 64 , 65 ] including the human MuHV-4 ortholog, KSHV [ 66 , 67 ]. Although MuHV-4 myeloid infection is sparse at steady state [ 68 ], inefficient ex vivo and not prominent in disease states, it is important for host entry, lymph node colonization [ 69 ] and systemic spread [ 27 ].…”

Simian Immunodeficiency Virus Infection and Mucosal Immunity

“…Possible mechanisms for mucosal SIV transmission across the intact squamous epithelium involve the interaction of virus with dendritic cells (DCs) and/or CD4 + CCR5 + T cells in the superficial mucosa. DCs are potent antigenpresenting cells (APCs) that express CD4 and MHC class II (Hu et al, 1998;Teleshova et al, 2013). A subset of immature DCs called Langerhans cells are abundant in the cervix and vaginal epithelium of humans (Hussain and Lehner, 1995;Bjercke et al, 1983;Morris et al, 1983;Turville et al, 2004) and macaques (Miller et al, 1992b;Hu et al, 1998;Poonia et al, 2006).…”

“…Rectal and colon tissues are also densely populated with T cells that express CD4 and CCR5, which are susceptible to HIV and SIV infection (Shattock and Moore, 2003;Mowat and Viney, 1997). Hence, any breakdown in epithelial integrity obviously allows HIV to directly access and infect target cells in this mucosal site (Pope and Haase, 2003;Teleshova et al, 2013).…”

“…Thus, a possible mechanism of mucosal SIV infection involves the capture of viral particles on the vaginal lumenal surface by DC processes expressing one or more MCLR. Once the virus has been captured, the immature DC then migrates and presents the virus to the underlying lymphoid cells of the lamina propria, which contain abundant CD4 + and CCR5 + T cells, macrophages, and DCs that support infection and local viral amplification (Teleshova et al, 2013;Hladik and Mcelrath, 2008;Xu et al, 2013b;Haase, 2011).…”

Nonhuman Primate Models of HIV Transmission

“…DCs can capture infectious HIV/SIV and transfer it to CD4 + T cells and also can become infected, synthesizing new virions, which are then transferred to CD4 + T cells. Thus, DCs play an important role in amplifying HIV and SIV infection and macaque DC biology largely mimics that of human DCs (Teleshova et al 2013).…”