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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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Effect of amino acid changes on the receptor activity of common marmoset (CJ) CD4 or squirrel monkey (SS) CD4. Cf2Th cells were transfected with plasmids encoding human CCR5 and the wild-type common marmoset (CJ) or squirrel monkey (SS) CD4 proteins, or the indicated mutant CD4 proteins. The cells were then incubated with recombinant, EGFP-expressing HIV-1 bearing the ADA, JR-FL, or YU2 envelope glycoproteins. After 48 h, cells were assayed for EGFP expression, as described in the Fig. 3 legend.
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fig9: Effect of amino acid changes on the receptor activity of common marmoset (CJ) CD4 or squirrel monkey (SS) CD4. Cf2Th cells were transfected with plasmids encoding human CCR5 and the wild-type common marmoset (CJ) or squirrel monkey (SS) CD4 proteins, or the indicated mutant CD4 proteins. The cells were then incubated with recombinant, EGFP-expressing HIV-1 bearing the ADA, JR-FL, or YU2 envelope glycoproteins. After 48 h, cells were assayed for EGFP expression, as described in the Fig. 3 legend.

Mentions: We wished to examine whether the alterations in glutamine 48 and glutamine 59 of common marmoset CD4 that restored gp120 binding would also allow more efficient function as an HIV-1 receptor. Cf2Th cells transiently expressing human CD4 or CJ CD4 variants along with human CCR5 were incubated with recombinant HIV-1 bearing the ADA, JR-FL, or YU2 HIV-1 envelope glycoproteins. Measurement of EGFP in the target cells revealed that, as expected, cells expressing human CD4 allowed more efficient infection than cells expressing the wild-type CJ CD4 molecule (Fig. 9 , top panel). Compared with cells expressing the wild-type CJ CD4 protein, cells expressing the Q48P and Q59R variants supported more efficient virus infection. Cells expressing the double mutant (CJ CD4 Q48P/Q59R) were infected with efficiencies ranging from 50–80 percent of that seen for cells expressing human CD4.


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)

Effect of amino acid changes on the receptor activity of common marmoset (CJ) CD4 or squirrel monkey (SS) CD4. Cf2Th cells were transfected with plasmids encoding human CCR5 and the wild-type common marmoset (CJ) or squirrel monkey (SS) CD4 proteins, or the indicated mutant CD4 proteins. The cells were then incubated with recombinant, EGFP-expressing HIV-1 bearing the ADA, JR-FL, or YU2 envelope glycoproteins. After 48 h, cells were assayed for EGFP expression, as described in the Fig. 3 legend.
© Copyright Policy
Related In: Results  -  Collection

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

fig9: Effect of amino acid changes on the receptor activity of common marmoset (CJ) CD4 or squirrel monkey (SS) CD4. Cf2Th cells were transfected with plasmids encoding human CCR5 and the wild-type common marmoset (CJ) or squirrel monkey (SS) CD4 proteins, or the indicated mutant CD4 proteins. The cells were then incubated with recombinant, EGFP-expressing HIV-1 bearing the ADA, JR-FL, or YU2 envelope glycoproteins. After 48 h, cells were assayed for EGFP expression, as described in the Fig. 3 legend.
Mentions: We wished to examine whether the alterations in glutamine 48 and glutamine 59 of common marmoset CD4 that restored gp120 binding would also allow more efficient function as an HIV-1 receptor. Cf2Th cells transiently expressing human CD4 or CJ CD4 variants along with human CCR5 were incubated with recombinant HIV-1 bearing the ADA, JR-FL, or YU2 HIV-1 envelope glycoproteins. Measurement of EGFP in the target cells revealed that, as expected, cells expressing human CD4 allowed more efficient infection than cells expressing the wild-type CJ CD4 molecule (Fig. 9 , top panel). Compared with cells expressing the wild-type CJ CD4 protein, cells expressing the Q48P and Q59R variants supported more efficient virus infection. Cells expressing the double mutant (CJ CD4 Q48P/Q59R) were infected with efficiencies ranging from 50–80 percent of that seen for cells expressing human CD4.

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