Evidence for Human Immunodeficiency Virus Type 1 Replication In Vivo in CD14
            <sup>+</sup>
            Monocytes and Its Potential Role as a Source of Virus in Patients on Highly Active Antiretroviral Therapy

Cordero

Cytometry Part B Clinical

et al. 2006

Background: HIV-1 infection has been associated with high expression of CD38 on peripheral blood (PB) CD81 and CD41 T-cells, which has been related with poor prognosis in untreated HIV-11 patients. In turn, CD38 expression on PB monocytes from HIV-11 individuals and its behavior after starting antiretroviral therapy (ART) have been poorly studied.Methods: CD38 expression on PB CD81 and CD41 T-lymphocytes and monocytes was prospectively analyzed in 30 ART-naive HIV-11 patients, using a quantitative multiparameter flow cytometry approach. Patients were tested prior to therapy, and at weeks 12, 14, 18, 112, and 152 after ART.Results: Prior to ART, CD38 expression was significantly increased on PB CD81 and CD41 T-cells and monocytes; despite a significant decrease after ART, CD38 expression remained abnormally high on PB CD81 T-cells and monocytes, even after one year of therapy, in the absence of detectable plasma viral load. The ART-induced early changes on CD38 expression by PB T-cells and monocytes differed among the cell subsets analyzed and patient groups, probably reflecting an interaction between the direct effects of therapy and a redistribution of the PB compartments of T-cells and monocytes. Hierarchical clustering analysis showed that the overall pattern of changes in CD38 expression observed early after starting ART was predictive of a better response to therapy, not only for PB CD81 T-cells, but also for CD41 T-cells and monocytes. Accordingly, those HIV-11 patients, who experienced a more pronounced increase in CD38 expression on both PB CD41 T-cells and monocytes after 2 weeks of ART, showed a more rapid viral clearance, which might reflect decreased HIV-1 replication in lymph nodes and other tissues, and a partial restoration of hematopoiesis.Conclusions: Combined quantitative measurement of CD38 expression on PB monocytes, and CD81 and CD41 T-cells is a more useful tool for monitoring HIV-11 patients under ART, rather than quantitation of CD38 expression on PB CD81 T-lymphocytes alone. q

Section: Discussionmentioning

confidence: 64%

Relationship between CD38 expression on peripheral blood T‐cells and monocytes, and response to antiretroviral therapy: A one‐year longitudinal study of a cohort of chronically infected ART‐naive HIV‐1+ patients

Cordero

Cytometry Part B Clinical

et al. 2006

The Journal of Immunology

“…Our laboratory and others have shown that, even in individuals with viral loads suppressed below detection for prolonged periods of time, HIV-1 continues to replicate at very low levels in monocytes and that infected monocytes can transmit HIV-1 to other susceptible cells (12,13,17). These data suggest that these cells are potentially important for the rebound of viral replication upon the interruption or cessation of antiretroviral therapy and in the dissemination of the virus to other tissues.…”

Section: Discussionmentioning

confidence: 78%

“…Our data are supported by a study of a cohort of HIV-1-infected, untreated pregnant women in Malawi whose CD16 ϩ monocytes were also shown to be preferentially infected with HIV-1 (most likely subtype C) (A. Jaworowski, accepted for publication). We and others have previously established that the persistence of HIV-1 in monocytes is not due to mutations associated with antiretroviral resistance (12,13,17). The detection of HIV-1 DNA within monocyte subsets was unlikely to be due to the presence of infected T cells contaminating the monocyte preparations, as selected experiments showed Ͻ0.01% T cell contamination.…”

Section: Discussionmentioning

confidence: 92%

“…It is well established that a replication-competent virus may be recovered from circulating peripheral blood monocytes of HIV-1-infected individuals, including those receiving HAART and who have maintained viral loads below detectable limits (Ͻ50 HIV-1 RNA copies per milliliter of plasma) for prolonged periods (12,13). The fact that monocytes remain in circulation for up to 3 days (14) suggests ongoing recent infection of these cells or their precursors (5); this is supported by the detection of labile unintegrated circularized forms of viral DNA (2-long terminal repeat (LTR) circles) (13,15,16), multiply spliced viral mRNA species in freshly isolated monocytes (13), and viral evolution within this compartment (17). Strains of HIV-1 that infect cells of the macrophage lineage typically use CCR5 as a coreceptor for viral entry, and increasing CCR5 expression on monocytes during differentiation correlates with the permissiveness of these cells to infection (18,19).…”

mentioning

confidence: 83%

See 1 more Smart Citation

The CD16+ Monocyte Subset Is More Permissive to Infection and Preferentially Harbors HIV-1 In Vivo

Ellery

Tippett

Chiu

et al. 2007

299

276

HIV-1 persists in peripheral blood monocytes in individuals receiving highly active antiretroviral therapy (HAART) with viral suppression, despite these cells being poorly susceptible to infection in vitro. Because very few monocytes harbor HIV-1 in vivo, we considered whether a subset of monocytes might be more permissive to infection. We show that a minor CD16+ monocyte subset preferentially harbors HIV-1 in infected individuals on HAART when compared with the majority of monocytes (CD14highCD16−). We confirmed this by in vitro experiments showing that CD16+ monocytes were more susceptible to CCR5-using strains of HIV-1, a finding that is associated with higher CCR5 expression on these cells. CD16+ monocytes were also more permissive to infection with a vesicular stomatitis virus G protein-pseudotyped reporter strain of HIV-1 than the majority of monocytes, suggesting that they are better able to support HIV-1 replication after entry. Consistent with this observation, high molecular mass complexes of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) were observed in CD16+ monocytes that were similar to those observed in highly permissive T cells. In contrast, CD14highCD16− monocytes contained low molecular mass active APOBEC3G, suggesting this is a mechanism of resistance to HIV-1 infection in these cells. Collectively, these data show that CD16+ monocytes are preferentially susceptible to HIV-1 entry, more permissive for replication, and constitute a continuing source of viral persistence during HAART.

“…Before entering the tissues and differentiating into macrophages, monocytes briefly circulate in peripheral blood (28,29). Several studies indicate that circulating monocytes also serve as a viral reservoir in infected individuals (15)(16)(17)33). The infection of circulating monocytes in vivo is at odds with in vitro studies, where monocytes acquire the ability to support productive viral infection only after their differentiation to macrophages (2,4,5,19,20,23,25).…”

mentioning

confidence: 65%

Characterization of Restrictions to Human Immunodeficiency Virus Type 1 Infection of Monocytes

Triques

Stevenson

2004

J Virol

Tissue macrophages are an important cellular reservoir for replication of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. In vitro, the ability of macrophages to support viral replication is differentiation dependent in that precursor monocytes are refractory to infection. There is, however, no consensus as to the exact point at which infection is restricted in monocytes. We have revisited this issue and have compared the efficiencies of early HIV-1 replication events in monocytes and in differentiated macrophages. Although virus entry in monocytes was comparable to that in differentiated macrophages, synthesis of full-length viral cDNAs was very inefficient. Relative to differentiated macrophages, monocytes contained low levels of dTTP due to low thymidine phosphorylase activity. Exogenous addition of D-thymidine increased dTTP levels to that in differentiated macrophages but did not correct the reverse transcription defect. These results point to a restriction in monocytes that is independent of reverse transcription precursors and suggest that differentiation-dependent cellular cofactors of reverse transcription are rate limiting in monocytes.