Dendritic Cells Are Less Susceptible to Human Immunodeficiency Virus Type 2 (HIV-2) Infection than to HIV-1 Infection

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) has been documented in vivo and may be an important contributor to HIV-1 transmission and pathogenesis. HIV-1-specific CD4+ T cells respond to HIV antigens presented by HIV-1-infected DCs and in this process become infected, thereby providing a mechanism through which HIV-1-specific CD4+ T cells could become preferentially infected in vivo. HIV-2 disease is attenuated with respect to HIV-1 disease, and host immune responses are thought to be contributory. Here we investigated the susceptibility of primary myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to infection by HIV-2. We found that neither CCR5-tropic primary HIV-2 isolates nor a lab-adapted CXCR4-tropic HIV-2 strain could efficiently infect mDCs or pDCs, though these viruses could infect primary CD4+ T cells in vitro. HIV-2-exposed mDCs were also incapable of transferring virus to autologous CD4+ T cells. Despite this, we found that HIV-2-specific CD4+ T cells contained more viral DNA than memory CD4+ T cells of other specificities in vivo. These data suggest that either infection of DCs is not an important contributor to infection of HIV-2-specific CD4+ T cells in vivo or that infection of DCs by HIV-2 occurs at a level that is undetectable in vitro. The frequent carriage of HIV-2 DNA within HIV-2-specific CD4+ T cells, however, does not appear to be incompatible with preserved numbers and functionality of HIV-2-specific CD4+ T cells in vivo, suggesting that additional mechanisms contribute to maintenance of HIV-2-specific CD4+ T-cell help in vivo.

Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes

“…The antibody used (KC57) has previously been shown to be specific for both HIV-2 Gag and HIV-1 Gag (35). We further confirmed the ability of the antibody to efficiently detect HIV-2 Gag by flow cytometry in activated PBMCs infected with the HIV-2 strains used in the current study (see Fig.…”

SAMHD1 Restricts HIV-1 Cell-to-Cell Transmission and Limits Immune Detection in Monocyte-Derived Dendritic Cells

“…The HIV-2 reverse transcriptase probably has a lower affinity for dNTPs (50), which may be detrimental for this virus in noncycling cells. It has been reported that DCs are less susceptible to HIV-2 than to HIV-1, when the infection is performed with cell-free virions (55). It will be worth examining whether HIV-2 more efficiently infects MDDCs by cellto-cell transmission and, if so, to evaluate the impact of Vpx on this phenomenon.…”

Preservation of Lymphopoietic Potential and Virus Suppressive Capacity by CD8+ T Cells in HIV-2–Infected Controllers

“…This requires further investigation because other groups have reported that dendritic cells are refractory to HIV-2 infection, which could in turn, restrict HIV-2 replication (65,66). Overall, an enhanced sensitivity of HIV-2 to host restriction factors may be crucial in limiting its replication initially, preventing further damage to the host immune system, providing the necessary window of opportunity for the subsequent induction and enactment of an effective T cell response that establishes and maintains control of the virus.…”