Cell reservoirs in lymph nodes infected with HIV-1 subtype E differ from subtype B: identification by combined in situ polymerase chain reaction and immunohistochemistry

Abstract

In Thailand, the predominant HIV subtype is E, rather than subtype B as in North America and Europe. Subtype E has the ability to replicate in vitro in Langerhans cells. We hypothesized that this cell type might constitute a reservoir for the HIV virus in infected lymph nodes. We examined lymph nodes from 25 HIV-1 subtype E-infected patients to determine the immunophenotype of HIV-1-infected cells, their numbers and their distribution. The presence of HIV was detected either by in situ reverse transcriptase-polymerase chain reaction or immunoperoxidase. Cell identity was determined by double labelling using alkaline phosphatase-based immunohistochemistry. The majority of HIV-infected cells in the lymph nodes were Langerhans cells (CD1a þ S100 þ ) and Langerhans-related dendritic cells (p55 þ S100 þ ). These cells were located in the paracortical areas of lymph nodes, with a few cells scattered at the edges of germinal centers, but were absent from germinal centers themselves, in contrast to the reported distribution of subtype B virus. In addition, multinucleated giant cells were significantly more common in HIV-infected nodes (64%) compared to controls (4%) (P ¼ 0.00002). In conclusion, Langerhans histiocytes and related cells are reservoirs for HIV subtype E in lymph nodes. Disrupting the pathway of infection of Langerhans cells and related cells may be a viable strategy to interfere with transmission of HIV subtype E.

HIV-1 Clade B Tat, but Not Clade C Tat, Increases X4 HIV-1 Entry into Resting but Not Activated CD4+ T Cells

“…Furthermore, although both Tat proteins bind CXCR4 with the same K d , neither is able to induce a transient calcium flux in primary CD4 ϩ T cells (16) or induce CD4 ϩ T cell chemotaxis. 3 In this study, we show that B Tat up-regulates the expression of CXCR4 on the surface of resting CD4 ϩ T cells within 4 h through a dose-and CCR2b-dependent mechanism in a manner similar to CCL2 (42) that does not require de novo protein synthesis but involves the relocation of preexisting CXCR4 to the cell surface combined with a decrease in CXCR4 internalization. However, the mutation found in C Tat renders it unable to bind CCR2b (16) and subsequently unable to up-regulate CXCR4 expression on CD4 ϩ T cells.…”

“…Globally, over 50% of all infections are caused by clade C, whereas clade B, the most studied clade, represents just 10% of all infections but is dominant in both Europe and North America. Recent research has shown that the different clades and CRF of HIV-1 have biological differences with respect to transmission (2), replication (3), and disease progression (4,5). Moreover, the HIV-1 proteins gp120 (6), Nef (7,8), Vif, Vpr, Vpu (9,10), and Tat (11)(12)(13)(14)(15)(16)(17)(18)(19) show clade and isotype-specific properties at both the molecular and biological levels.…”

Human Immunodeficiency Virus Type 1 Subtype C Tat Fails To Induce Intracellular Calcium Flux and Induces Reduced Tumor Necrosis Factor Production from Monocytes

“…Among the defined effects, subtype B Tat has been shown to be chemotactic for monocytes (2,3,50) and microglial cells (26) and to induce the production of tumor necrosis factor (TNF), chemokine (C-C motif) ligand 2 (CCL2) (previously known as monocyte chemotactic protein 1 [MCP-1]), and interleukin-6 (IL-6) from monocytes (25,59,87). However, recent research has shown that the different genetic subtypes and recombinant forms of HIV-1 have biological differences with respect to transmission, replication, and disease progression (14,47,74,85). Moreover, different subtypes of Tat have different in vitro effects (17,18,27,28,57,62,66,67,76).…”

Targeting persistent HIV infection: Where and how, if possible?

“…For example, whole HIV-1 virions bound extracellularly to follicular dendritic cells (FDC) in germinal centers (GC) of lymphoid tissues (LT) have been observed [35]. Further still, in those organs associated with extensive lymphoid tissues such as the gut-associate lymphoid tissue (GALT), HIV eradication has been noted to be a challenge [35][36][37][38][39][40][41][42][43][44] regardless of the time-periods of HAART use. Additionally, various recent studies reporting on the genomic compartmentalization of HIV-1 in blood and other organs have also emerged.…”

“…Heath et al [51], however, failed to demonstrate similar genetic compartmentalization of HIV-1 between lung and blood. [42][43][44] have used in situ polymerase chain reaction and immunohistochemistry to show that the cell hide-out in lymph nodes infected with HIV-1 subtype E differ from that of subtype B.…”