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(Journal of Leukocyte Biology. 2000;68:360-365.)
© 2000 by Society for Leukocyte Biology

Biological parameters of HIV-1 infection in primary intestinal lymphocytes and macrophages

Phillip D. Smith*,§, Gang Meng*, Marty T. Sellers{dagger}, Tina S. Rogers{ddagger} and George M. Shaw||

Departments of Medicine (
* Gastroenterology and
{ddagger} Rheumatology) and Surgery (
{dagger} Transplantation), University of Alabama at Birmingham;
§ Birmingham Veterans Affairs Medical Center and the
|| Howard Hughes Medical Institute, Birmingham

Correspondence: Phillip D. Smith, M.D., Department of Medicine (Gastroenterology and Hepatology), UAB, 703 19th Street South, Birmingham, AL 35294.


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ABSTRACT
 
Mucosal surfaces are the portal of entry for most HIV-1 infections and play an important role in disease pathogenesis. To characterize the biological parameters of HIV-1 infection in mucosal cells, we used purified lamina propria lymphocytes and macrophages from normal human small intestine to determine the distribution of the HIV-1 receptor and coreceptors on intestinal mononuclear cells and the permissiveness of these cells to HIV-1 infection. Lamina propria lymphocytes expressed CD4, CCR5, and CXCR4. In contrast, lamina propria macrophages expressed CD4 but not CCR5 or CXCR4. Intestinal lymphocytes supported replication by R5 and X4 isolates of HIV-1, but lamina propria macrophages were permissive to neither. RANTES, macrophage inflammatory protein-1{alpha} (MIP-1{alpha}), and MIP-1ß inhibited infection of intestinal lymphocytes by BaL, indicating that R5 infection of the intestinal lymphocytes was mediated by CCR5. Thus, resident lamina propria lymphocytes, not macrophages, are the target mononuclear cell for HIV-1 infection in the intestinal mucosa during early HIV-1 infection.

Key Words: mucosa • lamina propria • CCR5 • CXCR4


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INTRODUCTION
 
Mucosal surfaces play a fundamental role in the pathogenesis of HIV-1 disease [1 ]. First, the gastrointestinal tract mucosa is the body surface through which HIV-1 enters the host in homosexual and vertical transmission. During vertical transmission, the upper gastrointestinal tract mucosa is particularly important, providing the site of virus translocation after the fetus or infant swallows HIV-1-infected amniotic fluid in utero, infected blood or cervical secretions intrapartum, or infected breast milk postpartum [2 ]. Second, the mucosa likely participates in the selection of the genotypic and phenotypic minor variants that are transmitted in acute infections. Third, the gastrointestinal tract mucosa is the largest lymphoid organ in the body [3 ], containing the largest number of lymphocytes and macrophages of any body organ [4 ]. Consequently, the enteric mucosa may be an important reservoir for HIV-1-infected mononuclear cells [5 ]. Moreover, the local abundance of cytokines [6 ] and microbial agents [7 ] capable of up-regulating HIV-1 expression [8 , 9 ] suggests that the mucosa is also a potential site of high-level HIV-1 production. Fourth, the local and systemic immunosuppression induced by HIV-1 infection predisposes the gastrointestinal tract to a complex array of opportunistic infections [7 ], resulting in substantial morbidity in the majority of persons who develop AIDS [10 ].

After HIV-1 inoculated onto a mucosal surface crosses the epithelium, likely by transcytosis [11 ], it encounters lamina propria mononuclear cells. These cells, or possibly epithelial cells, presumably select from the pool of inoculated variants the macrophage-tropic species that are transmitted in nearly all mucosally acquired HIV-1 infections [12 13 14 15 ]. This selection is likely receptor-mediated, but the distribution of CD4 (the primary receptor for HIV-1), CCR5 [the coreceptor for macrophage-tropic (R5) viruses] and CXCR4 [the coreceptor for lymphocyte-tropic (X4) viruses] on intestinal lamina propria cells has not been fully elucidated. In addition, the biological parameters of HIV-1 replication in mucosal mononuclear cells have not been fully characterized. Therefore, to elucidate the role of mucosal mononuclear cells in HIV-1 disease, we have initiated a series of studies that seek to characterize intestinal (lamina propria) lymphocytes and macrophages for HIV-1 receptor and coreceptor expression and susceptibility to infection by R5 and X4 HIV-1.


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RESIDENT INTESTINAL LYMPHOCYTES AND MACROPHAGES
 
Current concepts regarding virological events in the mucosa during HIV-1 disease have been extrapolated largely from studies of the interaction between blood mononuclear cells and HIV-1. However, lamina propria lymphocytes and macrophages differ phenotypically and functionally in many regards from blood lymphocytes and monocytes [16 , 17 ]. Consequently, information acquired from the study of blood mononuclear cells and HIV-1 does not accurately reflect mucosal cell-HIV-1 events. Therefore, to study the interaction between primary mucosal cells and HIV-1, we developed a technique to isolate and purify lamina propria lymphocytes and macrophages from normal human small intestinal mucosa. Lamina propria lymphocytes and macrophages were isolated from jejunal tissue sections from organ transplantation donors without intestinal or immunological diseases by tissue digestion using the neutral protease Dispase [18 ]. The lamina propria mononuclear cells were then separated by counterflow centrifugal elutriation into highly purified populations of lymphocytes and macrophages [18 , 19 ]. The intestinal lymphocytes displayed typical lymphocyte morphology and phenotype [18 ]. Intestinal macrophages isolated and purified by the same technique displayed the size distribution, morphological features, ultrastructure, phagocytic activity, and phenotype of macrophages [18 ]. Blood lymphocytes and monocytes from the same donors were purified by counterflow centrifugal elutriation [19 ] and then treated with neutral protease according to the tissue digestion protocol in order for all cell populations to be treated similarly before study.

Purified intestinal lymphocytes were routinely >=95% CD3+CD103+ and blood lymphocytes routinely >=95% CD3+, and neither population contained detectable macrophages or monocytes, respectively (Fig. 1 ). Approximately 1% of intestinal lymphocytes were B cells, and about 5% of blood lymphocytes were B cells. Conversely, HLA-DR+CD13+ intestinal macrophages, which are CD14- [17 , 18 ], and CD14+HLA-DR+CD13+ blood monocytes contained no detectable lymphocytes (Fig. 1) . The intestinal cells did not express CD83 or display ultrastructural characteristics of dendritic cells before or after treatment with optimal concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor {alpha} (TNF-{alpha}), and interleukin-4 (IL-4).



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  		Figure 1. Purity of intestinal lymphocytes and macrophages and blood lymphocytes and monocytes. Cells were isolated from segments of normal human intestine by enzyme digestion, purified by elutriation, and analyzed before culture for the indicated surface antigen by flow cytometry. Results from a representative donor show fluorescence profiles for purified populations of cells stained with CD-specific antibodies (solid lines), HLA-DR, or isotype-matched control antibody (dotted line).


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REDUCED PERMISSIVENESS OF INTESTINAL MACROPHAGES TO HIV-1 INFECTION
 
We recently showed that intestinal macrophages require 1,000-fold more virus to establish infection in vitro than monocyte-derived macrophages (Fig. 2 ) [20 ]. This is consistent with the remarkably low prevalence (0.06%) of HIV-1 mRNA-expressing macrophages among lamina propria mononuclear cells in the gastrointestinal tract mucosa of patients with AIDS [5 ]. The marked reduction in the permissiveness of intestinal macrophages to HIV-1 infection was not caused by the isolation procedure or reduced CD4 expression. Instead, intestinal macrophages expressed almost no detectable CCR5 (Fig. 3A ), the principal coreceptor for R5 (macrophage-tropic) viruses, although both intestinal macrophages and blood monocytes contained comparable levels of CCR5 mRNA (Fig. 3B) . Exposure of monocyte-derived macrophages to HIV-1 or gp120 lead to increased surface expression of CCR5, but exposure of intestinal macrophages to either HIV-1 or gp120 did not (Fig. 3C) . These findings suggested that the markedly impaired permissiveness of intestinal macrophages to HIV-1 was due to the near absence of macrophage surface CCR5.



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  		Figure 2. Kinetics and levels of p24 antigen production by HIV-1-inoculated monocytes (blood-derived macrophages) and intestinal (lamina propria) macrophages. Cells were cultured for 5 days and then inoculated with serial dilutions of the indicated HIV-1 R5 (ADA, DJV, or BaL) or X4 (IIIB) isolate and monitored for p24 production. (Reproduced with permission from ref. 20 ).



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  		Figure 3. CCR5 expression on monocytes (blood-derived macrophages) and intestinal (lamina propria) macrophages. Cells were analyzed (A) by dual fluorescence flow cytometry for CCR5/CD13 and CCR5/HLA-DR, (B) by reverse-transcriptase polymerase chain reaction for CCR5 mRNA, and (C) by flow cytometry after a 24-h incubation with media alone, LPS (10 µg/mL), HIV-1 (BaL: TCID50 1,000/2.5 x 106 cells/mL), or gp120 (1 µg/mL). Bars represent the mean ± SD percent of CCR5-positive cells for three independent experiments. Insets in upper panels of A show the contour plots for the isotype-matched control antibody. (Reproduced with permission from ref. 20 .)

The findings also suggested a paradox in which intestinal macrophages are down-regulated for permissiveness to HIV-1 [20 ], yet acutely transmitted HIV-1 species are nearly always macrophage-tropic [12 13 14 15 ]. Therefore, to confirm the absence of CCR5 on intestinal macrophages and to elucidate the potential role of intestinal lymphocytes in early HIV-1 infection, we characterized purified primary intestinal lymphocytes and macrophages from the same donors for surface CD4, CCR5, and CXCR4 expression and then determined the permissiveness of the cells to macrophage-tropic and lymphocyte-tropic HIV-1.


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INTESTINAL LYMPHOCYTES, NOT MACROPHAGES, EXPRESS CCR5 AND CXCR4
 
Because intestinal macrophages appeared to lack CCR5, we next investigated primary intestinal lymphocytes for surface CCR5 and CXCR4 expression [21 ]. Among fresh intestinal lymphocytes purified from a representative donor, 10% expressed surface CD4, 92% CCR5, and 86% CXCR4 (Fig. 4 ). Among intestinal macrophages freshly isolated from the same donor, 9% expressed CD4, but, in sharp contrast to the intestinal lymphocytes, none expressed detectable CCR5 or CXCR4 (Fig. 4) . In addition, incubation of the macrophages with optimal doses of M-CSF, GM-CSF, IL-6, phorbol myristate acetate (PMA), or lipopolysaccharide (LPS) for 24 h did not induce expression of either coreceptor. Blood lymphocytes and monocytes from the same donor expressed CD4 and both CCR5 and CXCR4 (Fig. 4) . The presence of CCR5 on blood monocytes (and on the intestinal and blood lymphocytes) from the same donor indicated that the absence of surface CCR5 on intestinal macrophages was not due to expression of the {Delta}32 CCR5 deletion allele. The frequencies of CD4+, CCR5+, and CXCR4+ cells in populations of purified intestinal and unmatched blood mononuclear cells from additional donors (Table 1 ) confirmed the presence of CCR5 and CXCR4 on each cell type except the intestinal macrophages.



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  		Figure 4. HIV-1 receptor and coreceptor expression on intestinal and blood mononuclear cells. Intestinal lymphocytes and macrophages and blood lymphocytes and monocytes from the same donor were purified and stained for CD4, CCR5, and CXCR4 within 2 h of isolation. The cells were subsequently analyzed for surface CD4, CCR5, and CXCR4 by flow cytometry.


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  		Table 1. Percent of Intestinal and Blood Mononuclear Cells that Express CD4, CCR5, and CXCR4


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INTESTINAL LYMPHOCYTES, NOT MACROPHAGES, SUPPORT R5 AND X4 HIV-1 REPLICATION
 
Having shown that intestinal lymphocytes express CD4, CCR5, and CXCR4 and that intestinal macrophages express only CD4, we next investigated the susceptibility of these populations to HIV-1 infection [21 ]. Intestinal lymphocytes (cultured 2 days with phytohemagglutinin 5 µg/mL and IL-2 24 U/mL) and macrophages (cultured 5 days in M-CSF 1,000 U/mL) were inoculated in parallel with R5 (BaL) and X4 (IIIB) isolates of HIV-1 (TCID50 10,000 each). Intestinal lymphocytes supported replication by both BaL and IIIB (Fig. 5 , left), consistent with their CCR5+CXCR4+ phenotype. In contrast, intestinal macrophages, which displayed no detectable CCR5 or CXCR4, were permissive to neither BaL nor IIIB (Fig. 5 , left). Intestinal macrophages also did not support replication by additional R5 laboratory isolates (ADA and DJV; TCID50 10,000) and primary clinical isolates (MDR 24 and JOEL; TCID50 500; Fig. 6 ). Furthermore, culturing the macrophages with GM-CSF, TNF-{alpha}, IL-6, PMA, or LPS during or after exposure of the cells to HIV-1 did not result in detectable p24 production.



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  		Figure 5. Levels of p24 antigen production in cultures of intestinal and blood mononuclear cells inoculated with HIV-1. Intestinal lymphocytes and macrophages (left panel) and blood lymphocytes and monocyte-derived macrophages (right panel) isolated from the same donor were cultured for either 2 days (lymphocytes) or 5 days (monocytes/macrophages) and then inoculated in parallel with an X4 isolate (IIIB) or an R5 isolate (BaL) of HIV-1 (TCID50 10,000 each) and monitored for p24 production.



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  		Figure 6. Peak p24 antigen production by intestinal macrophages and monocyte-derived macrophages inoculated with laboratory and primary isolates of HIV-1. Intestinal macrophages and blood monocytes isolated from the same donor were cultured for 5 days, inoculated with laboratory (ADA and DJV; TCID50 10,000) or primary (JOEL and MD24; TCID50 500) isolates of HIV-1 and then monitored for p24 production. Bars correspond to levels of peak p24 antigen production (day 16).

We next compared the level of HIV-1 replication in intestinal mononuclear cells with that of blood lymphocytes and monocyte-derived macrophages from the same donor. Similar to the intestinal lymphocytes, blood lymphocytes (cultured in the same conditions as the intestinal lymphocytes) supported HIV-1 replication by BaL and IIIB (Fig. 5 , right). Although intestinal lymphocytes were permissive to HIV-1, they produced less p24 antigen than infected blood lymphocytes. In sharp contrast, monocyte-derived macrophages inoculated with BaL produced high levels of p24 (peak 90,000 pg/mL), whereas intestinal macrophages inoculated with the same doses of HIV-1 produced no detectable p24 (Fig. 5 , right). Neither intestinal macrophages nor monocyte-derived macrophages supported IIIB replication, consistent with the absence of CXCR4 on the intestinal macrophages (Fig. 4 ; Table 1 ) and the lack of biological function of the CXCR4 receptor on blood monocytes [22 ]. Thus, intestinal lymphocytes, not macrophages, support HIV-1 replication.


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SUMMARY
 
The results summarized above suggest the following sequence of events in the intestinal mucosa before and during early HIV-1 infection. As circulating CCR5+CXCR4+ blood lymphocytes and monocytes traffic through the mucosa, they encounter local chemotactic signals that direct their migration into the lamina propria. Once in the mucosa, the cells encounter local bacterial products, such as LPS. The LPS binds to monocyte surface CD14, the receptor for complexes of LPS and LPS-binding protein, which activates the cells and causes down-regulation of CCR5 expression [23 ]. Lymphocytes, lacking CD14, would not be susceptible to the down-modulatory action of LPS. Also, differentiation of blood monocytes into macrophages may cause down-regulation of surface CXCR4 [24 ], offering a potential explanation, at least in part, for the impaired expression of CXCR4 on the macrophages. Whether human small intestinal macrophages differ from colonic macrophages in the expression of surface CCR5 and CXCR4 is not known. As the monocytes take up residence in the lamina propria and differentiate into macrophages, they also lose surface CD14 by mechanisms that are currently under investigation [17 ].

After HIV-1 inoculated onto a mucosal surface crosses the epithelium, it encounters CD4+ mononuclear cells in the underlying lamina propria. Whereas intestinal macrophages were presumed to be the initial target cell for R5 HIV-1 entry, the findings presented above indicate that the only resident mononuclear cells capable of supporting R5 viral replication in the mucosa are lamina propria lymphocytes, not macrophages. Although dendritic cells play an important role in the pathogenesis of early HIV-1 infection in extraintestinal lymphoid tissue [25 , 26 ], their role in intestinal HIV-1 infection is less likely since, as shown here, they appear not to be present in intestinal lamina propria. Dendritic cells are present in organized lymphoid structures (i.e., Peyer’s patches) of the mouse small intestine [27 ], but such structures are uncommon in the proximal small intestine of humans. Thus, the presence of CCR5 on intestinal lymphocytes and their susceptibility to R5 virus infection suggest that after initial selection, possibly by intestinal epithelial cells, the R5 species that enters the lamina propria first infects lymphocytes.

That intestinal lymphocytes, not macrophages, are permissive to HIV-1 infection is consistent with in vivo observations in both humans and macaques. As we have shown in humans with AIDS, mucosal macrophages productively infected with HIV-1 are rare, with a prevalence of 0.06% among lamina propria mononuclear cells [5 ]. In addition, the majority of cells containing HIV-1 mRNA in nongastrointestinal lymphoid tissue (e.g., tonsils) are not macrophages but other lymphoid mononuclear cells [28 ]. In macaques, simian immunodeficiency virus (SIV) inoculated intravenously [29 ], intravaginally [30 ], and orally [31 ] first infects mucosal lymphocytes and the subsequent local replication occurs predominantly in lymphocytes; infected intestinal macrophages are rare during early infection [29 30 31 ]. Also, CCR5+ macrophages constitute <1% of rectal lamina propria macrophages in macaques [32 ].

Thus, taken together, these findings indicate that resident macrophages play a less important role in the pathogenesis of early mucosal HIV-1 infection than previously suspected. Instead, intestinal lymphocytes appear to be the initial target cell for mucosally acquired R5 HIV-1 and the predominant source of HIV-1 production among resident mononuclear cells in the gastrointestinal tract mucosa.


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ACKNOWLEDGEMENTS
 
This study was supported by National Institutes of Health grants DK-47322, AI-41530, DE-72621, and by the Research Service of the Department of Veterans Affairs.


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REFERENCES
 
    1
  1. Smith, P. D., Wahl, P. D. (1999) Immunobiology of mucosal HIV-1 infection Ogra, P. R. Lamm, M. E. Bienenstock, J. Mestecky, J. Strober, W. McGhee, J. R. eds. Mucosal Immunology ,977 Academic San Diego.
    2. 2
  2. Li, L., Smith, P. D. (1996) Immunobiology of mucosal HIV-1 infection Curr. Op. Gastroenterol. 12,560-563
    3. 3
  3. Brandtzaeg, P. (1989) Overview of the mucosal immune system Curr. Top. Microbiol. Immunol. 146,13-25[Medline]
    4. 4
  4. Lee, S. H., Starkey, P. M., Gordon, S. (1984) Quantitative analysis of total macrophage content in adult mouse tissues: immunochemical studies with monoclonal antibody F4/80 J. Exp. Med. 161,475-489[Abstract/Free Full Text]
    5. 5
  5. Smith, P. D., Fox, C. H., Masur, H., Winter, H. S., Alling, D. W. (1994) Quantitative analysis of mononuclear cells expressing human immunodeficiency virus type-1 RNA in esophageal mucosa J. Exp. Med. 180,1541-1546[Abstract/Free Full Text]
    6. 6
  6. Smith, P. D., Saini, S. S., Raffeld, M., Manischewitz, J. F., Wahl, S. M. (1992) Cytomegalovirus induces expression of tumor necrosis factor by human monocytes and mucosal macrophages J. Clin. Invest. 90,1642-1648
    7. 7
  7. Smith, P. D. (1995) Intestinal infections in HIV-1 disease Blaser, M. J. Smith, P. D. Ravdin, J. I. Greenberg, H. B. Guerrant, R. L. eds. Infections of the Gastrointestinal Tract ,483 Raven New York.
    8. 8
  8. Peterson, P. K., Gekker, G., Chao, C. C., Hu, S., Edelman, C., Balfour, H. H., Verhoef, J. (1992) Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor-{alpha}-mediated mechanism J. Clin. Invest. 89,574-580
    9. 9
  9. Orenstein, J. M., Fox, C., Wahl, S. M. (1998) Macrophages as a source of HIV during opportunistic infections Science 276,1857-1861[Abstract/Free Full Text]
    10. 10
  10. Smith, P. D., Wilcox, C. M. (1999) Gastrointestinal complications of the acquired immunodeficiency syndrome Yamada, T. Alpers, D. H. Owyang, C. Powell, D. W. Laine, L. eds. Texrtbook of Gastroenterology ,2400 Lippincott Williams & Wilkins Philadelphia, PA.
    11. 11
  11. Bomsel, M. (1997) Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier Nat. Med. 3,42-47[Medline]
    12. 12
  12. Zhu, T., Mo, H., Wang, N., Nam, D. S., Cao, Y., Koup, R. A., Ho, D. D. (1993) Genotypic and phenotypic characterization of HIV-1 in patients with primary infection Science 261,1179-1181
    13. 13
  13. McNearney, T., Hornickova, Z., Markham, R., Birdwell, A., Arens, M., Saah, A., Ratner, L. (1992) Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease Proc. Natl. Acad. Sci. USA 89,10247-10251[Abstract/Free Full Text]
    14. 14
  14. Wolinsky, S. M., Wike, C. M., Korber, B. T. M., Hutto, C., Parks, W. P., Rosenblum, L. L., Kunstman, K. J., Furtado, M. R., Munoz, J. L. (1992) Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants Science 255,1134-1136[Abstract/Free Full Text]
    15. 15
  15. van’t Wout, A. B., Kootstra, N. A., Mulder-Kampinga, G. A., Albrecht-van Lent, N., Scherpbier, H. J., Veestra, J., Boer, K., Coutinho, R. A., Miedema, F., Schuitemaker, H. (1994) Macrophage-tropic variants initiate human immunodeficiency virus type I infection after sexual, parenteral, and vertical transmission J. Clin. Invest. 94,2060-2067
    16. 16
  16. Hurst, S. D., Coooper, C. J., Sitterding, S. M., Choi, J.-h., Jump, R. L., Levine, A. D., Barrett, T. A. (1999) The differentiated state of intestinal lamina porpria CD4+ T cells results in altered cytokine production, activation threshold and costimulatory requirements J. Immunol. 163,5937-5945[Abstract/Free Full Text]
    17. 17
  17. Smith, P. D., Mosteller-Barnum, M., Smythies, L. E., Sibley, D., Russell, M., Merger, M., Graham, M. F., Shimada, T., Kubagawa, H. (2000) Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J. Immunol. In press.
    18. 18
  18. Smith, P. D., Janoff, E. N., Mosteller-Barnum, M., Merger, M., Orenstein, J. M., Kearney, J. F., Graham, M. F. (1997) Isolation and purification of CD14-negative mucosal macrophages from normal human small intestine J. Immunol. Meth. 202,1-11[Medline]
    19. 19
  19. Wahl, L. M., Smith, P. D. (1991) Isolation of macrophages/monocytes from human peripheral blood and tissues Coligan, J. E. Kruisbeek, A. M. Marguilies, D. H. Shevach, E. M. Strober, W. eds. Current Protocols in Immunology 1,7.6.1-7.6.8 New York.
    20. 20
  20. Li, L., Meng, G., Graham, M. F., Shaw, G. M., Smith, P. D. (1999) Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5 Gastroenterology 116,1043-1053[Medline]
    21. 21
  21. Meng, G., Sellers, M. T., Mosteller-Barnum, M., Rogers, T. S., Shaw, G. M., Smith, P. D. (2000) Lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and are the primary target cell for HIV-1 in the intestinal mucosa. J. Infect. Dis. In press.
    22. 22
  22. Lapham, C. K., Zaitseva, M. B., Lee, S., Romanstseva, T., Golding, H. (1999) Fusion of monocytes and macrophges with HIV-1 correlates with biochemical properties of CXCR4 and CCR5 Nat. Med. 5,303-308[Medline]
    23. 23
  23. Sica, A., Saccani, A., Borsatti, A., Power, C. A., Wells, T. N. C., Luini, W., Polentarutti, N., Sozzani, S., Mantovani, A. (1997) Bacterial lipopolysaccharide rapidly inhibits expression of C-C chemokine receptors in human monocytes J. Exp. Med. 185,969-974[Abstract/Free Full Text]
    24. 24
  24. di Marzio, P., Tse, J., Landau, N. R. (1998) Chemokine receptor regulation and HIV type 1 tropism in monocyte-macrophges AIDS Res. Hum. Retrovir. 14,129-138[Medline]
    25. 25
  25. Frankel, S. S., Wenig, B. M., Burke, A. P., Mannan, P., Thompson, L. D. R., Abbondanzo, S. L., Nelson, A. M., Pope, M., Steinman, R. M. (1996) Replication of HIV-1 in dendritic cell-derived syncytia at the mucosal surface of the adenoid Science 72,115-117
    26. 26
  26. Haase, A. T., Henry, K., Zupancic, M., Sedgewick, G., Faust, A., Melroe, H., Cavert, W., Gebhard, K., Staskus, K., Zhang, Z.-Q., Dailey, P. J., Balfour, H. H., Erice, A., Perelson, A. S. (1996) Quantitative image analysis of HIV-1 infection in lymphoid tissue Science 274,985-989[Abstract/Free Full Text]
    27. 27
  27. Kelsall, B. L., Strober, W. (1996) Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer’s patch J. Exp. Med. 183,237-247[Abstract/Free Full Text]
    28. 28
  28. Cavert, W., Notermans, D. W., Staskus, K., Wietgrete, S. W., Zupancic, M., Gebhard, K., Henry, K., Zhang, Z-Q., Mills, R., McDade, H., Goudsmit, J., Danner, S. A., Haase, A. T. (1997) Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection Science 276,960-965[Abstract/Free Full Text]
    29. 29
  29. Veazey, R. S., DeMaria, M., Chalifoux, L. V., Shvetz, D. E., Pauley, D. R., Knight, H. L., Rosenzweig, M., Johnson, R. P., Desrosiers, R. C., Lackner, A. A. (1998) Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection Science 280,427-431[Abstract/Free Full Text]
    30. 30
  30. Zhang, Z.-Q., Schuler, T., Zupancic, M., Wietgrefe, S., Staskus, K. A., Reimann, K. A., Reinhart, T. A., Rogan, M., Cavert, W., Miller, C. J., Veazey, R. S., Notermans, D., Little, S., Dannear, S. A., Richman, D. D., Havlir, D., Wong, J., Jordan, H. L., Schacker, T. W., Racz, P., Tenner-Racz, K., Letvin, N. L., Wolinsky, S., Haase, A. T. (1999) Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells Science 286,1353-1357[Abstract/Free Full Text]
    31. 31
  31. Stahl-Henning, C., Steinman, R. M., Tenner-Racz, K., Pope, M., Stolte, N., Matz-Rensing, K., Grobschupff, G., Raschdorff, B., Hunsmann, G., Racz, P. (1999) Rapid infection of oral mucosa-associated lymphoid tissue with simian immunodeficiency virus Science 285,1261-1265[Abstract/Free Full Text]
    32. 32
  32. Zhang, L., He, T., Talal, A., Wang, G., Frankel, S. S., Ho, D. D. (1998) In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5 J. Virol. 72,5035-5045[Abstract/Free Full Text]



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