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Blockade of HIV-1 infection of New World monkey cells occurs primarily at the stage of virus entry.

LaBonte JA, Babcock GJ, Patel T, Sodroski J - J. Exp. Med. (2002)

Bottom Line: Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors.A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids found in human CD4, supported HIV-1 entry efficiently.Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Immunology & AIDS, JFB 824, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

ABSTRACT
HIV-1 naturally infects chimpanzees and humans, but does not infect Old World monkeys because of replication blocks that occur after virus entry into the cell. To understand the species-specific restrictions operating on HIV-1 infection, the ability of HIV-1 to infect the cells of New World monkeys was examined. Primary cells derived from common marmosets and squirrel monkeys support every phase of HIV-1 replication with the exception of virus entry. Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors. HIV-1 did not detectably bind or utilize squirrel monkey CD4 for entry, and marmoset CD4 was also very inefficient compared with human CD4. A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids found in human CD4, supported HIV-1 entry efficiently. The CXCR4 molecules of both marmosets and squirrel monkeys supported HIV-1 infection, but the CCR5 proteins of both species were only marginally functional. These results demonstrate that the CD4 and CCR5 proteins of New World monkeys represent the major restriction against HIV-1 replication in these primates. Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection.

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CD4 and CXCR4 expression levels in stable Cf2Th cell lines. Cf2Th cells stably expressing CD4 and CXCR4 of the indicated species were stained with Q4120 antibody (for CD4) and 12G5 antibody (for CXCR4). The 2D7 anti-CCR5 antibody was used as a negative control (shaded peak).
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fig6: CD4 and CXCR4 expression levels in stable Cf2Th cell lines. Cf2Th cells stably expressing CD4 and CXCR4 of the indicated species were stained with Q4120 antibody (for CD4) and 12G5 antibody (for CXCR4). The 2D7 anti-CCR5 antibody was used as a negative control (shaded peak).

Mentions: In the studies described above, low but reproducible levels of HIV-1 entry occurred in cells expressing the CD4 and CXCR4 receptors from common marmosets. To verify this observation, Cf2Th lines stably expressing both CD4 and CXCR4 derived from humans, squirrel monkeys, and common marmosets were established. Fig. 6 shows that these cell lines stain with the CD4-specific antibody Q4120 and the CXCR4-specific antibody 12G5; staining with the CCR5-specific antibody 2D7 was equivalent to that seen with an irrelevant antibody (data not shown). Recombinant HIV-1 containing either CXCR4-using HIV-1 envelope glycoproteins or the VSV G glycoprotein were incubated with the Cf2Th cell lines expressing human, squirrel monkey, or common marmoset CD4 and CXCR4 glycoproteins. 48 h later, EGFP-positive cells were visualized (Fig. 7) . Viruses with the HIV-1 envelope glycoproteins efficiently infected the cell line expressing the human receptors, and viruses with the VSV G glycoprotein infected all three cell lines efficiently. Cells expressing the squirrel monkey receptors were almost completely resistant to infection by viruses with the HIV-1 envelope glycoproteins. Some of these viruses, however, were able to infect the cells expressing common marmoset receptors at a low level. These results suggest that the CD4 and CXCR4 molecules of common marmosets can support the entry of HIV-1 with some X4 or R5X4 envelope glycoproteins, although these New World monkey receptors are much less efficient than their human homologues.


Blockade of HIV-1 infection of New World monkey cells occurs primarily at the stage of virus entry.

LaBonte JA, Babcock GJ, Patel T, Sodroski J - J. Exp. Med. (2002)

CD4 and CXCR4 expression levels in stable Cf2Th cell lines. Cf2Th cells stably expressing CD4 and CXCR4 of the indicated species were stained with Q4120 antibody (for CD4) and 12G5 antibody (for CXCR4). The 2D7 anti-CCR5 antibody was used as a negative control (shaded peak).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196058&req=5

fig6: CD4 and CXCR4 expression levels in stable Cf2Th cell lines. Cf2Th cells stably expressing CD4 and CXCR4 of the indicated species were stained with Q4120 antibody (for CD4) and 12G5 antibody (for CXCR4). The 2D7 anti-CCR5 antibody was used as a negative control (shaded peak).
Mentions: In the studies described above, low but reproducible levels of HIV-1 entry occurred in cells expressing the CD4 and CXCR4 receptors from common marmosets. To verify this observation, Cf2Th lines stably expressing both CD4 and CXCR4 derived from humans, squirrel monkeys, and common marmosets were established. Fig. 6 shows that these cell lines stain with the CD4-specific antibody Q4120 and the CXCR4-specific antibody 12G5; staining with the CCR5-specific antibody 2D7 was equivalent to that seen with an irrelevant antibody (data not shown). Recombinant HIV-1 containing either CXCR4-using HIV-1 envelope glycoproteins or the VSV G glycoprotein were incubated with the Cf2Th cell lines expressing human, squirrel monkey, or common marmoset CD4 and CXCR4 glycoproteins. 48 h later, EGFP-positive cells were visualized (Fig. 7) . Viruses with the HIV-1 envelope glycoproteins efficiently infected the cell line expressing the human receptors, and viruses with the VSV G glycoprotein infected all three cell lines efficiently. Cells expressing the squirrel monkey receptors were almost completely resistant to infection by viruses with the HIV-1 envelope glycoproteins. Some of these viruses, however, were able to infect the cells expressing common marmoset receptors at a low level. These results suggest that the CD4 and CXCR4 molecules of common marmosets can support the entry of HIV-1 with some X4 or R5X4 envelope glycoproteins, although these New World monkey receptors are much less efficient than their human homologues.

Bottom Line: Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors.A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids found in human CD4, supported HIV-1 entry efficiently.Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Immunology & AIDS, JFB 824, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

ABSTRACT
HIV-1 naturally infects chimpanzees and humans, but does not infect Old World monkeys because of replication blocks that occur after virus entry into the cell. To understand the species-specific restrictions operating on HIV-1 infection, the ability of HIV-1 to infect the cells of New World monkeys was examined. Primary cells derived from common marmosets and squirrel monkeys support every phase of HIV-1 replication with the exception of virus entry. Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors. HIV-1 did not detectably bind or utilize squirrel monkey CD4 for entry, and marmoset CD4 was also very inefficient compared with human CD4. A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids found in human CD4, supported HIV-1 entry efficiently. The CXCR4 molecules of both marmosets and squirrel monkeys supported HIV-1 infection, but the CCR5 proteins of both species were only marginally functional. These results demonstrate that the CD4 and CCR5 proteins of New World monkeys represent the major restriction against HIV-1 replication in these primates. Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection.

Show MeSH
Related in: MedlinePlus