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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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Ability of New World monkey CD4 to support entry of CXCR4-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CXCR4, or with New World monkey CD4 and either human or New World monkey CXCR4. Recombinant, EGFP-expressing HIV-1 bearing the indicated CXCR4-using HIV-1 envelope glycoproteins was incubated with the cells, and EGFP-positive cells were scored as described in the Fig. 3 legend. Human receptors were compared with those of squirrel monkeys (A) or common marmosets (B).
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fig4: Ability of New World monkey CD4 to support entry of CXCR4-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CXCR4, or with New World monkey CD4 and either human or New World monkey CXCR4. Recombinant, EGFP-expressing HIV-1 bearing the indicated CXCR4-using HIV-1 envelope glycoproteins was incubated with the cells, and EGFP-positive cells were scored as described in the Fig. 3 legend. Human receptors were compared with those of squirrel monkeys (A) or common marmosets (B).

Mentions: To compare the functionality of human and New World monkey CD4 molecules in supporting HIV-1 entry, Cf2Th cells expressing either human or New World monkey CD4 in combination with human or New World monkey CXCR4 were exposed to recombinant HIV-1 expressing EGFP, as described above. As was observed previously, cells expressing human CD4 and either SS or CJ CXCR4 proteins supported HIV-1 entry at roughly 50% the level seen for cells expressing human CD4 and human CXCR4 molecules (Fig. 4, A and B) . Cells expressing either SS or CJ CD4 did not support efficient infection regardless of the coexpression of human or New World monkey CXCR4 molecules. A small percentage of EGFP-positive cells was observed after infection of the cells expressing both marmoset receptors exposed to the recombinant KB9 virus (Fig. 4 B). This was consistently higher than the background associated with cells transfected only with the human CD4-expressing plasmid. Recombinant HIV-1 pseudotyped with the VSV G glycoprotein infected all of the cells efficiently (data not shown). These results indicate that the New World monkey CD4 molecules are not efficient HIV-1 receptors.


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)

Ability of New World monkey CD4 to support entry of CXCR4-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CXCR4, or with New World monkey CD4 and either human or New World monkey CXCR4. Recombinant, EGFP-expressing HIV-1 bearing the indicated CXCR4-using HIV-1 envelope glycoproteins was incubated with the cells, and EGFP-positive cells were scored as described in the Fig. 3 legend. Human receptors were compared with those of squirrel monkeys (A) or common marmosets (B).
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Ability of New World monkey CD4 to support entry of CXCR4-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CXCR4, or with New World monkey CD4 and either human or New World monkey CXCR4. Recombinant, EGFP-expressing HIV-1 bearing the indicated CXCR4-using HIV-1 envelope glycoproteins was incubated with the cells, and EGFP-positive cells were scored as described in the Fig. 3 legend. Human receptors were compared with those of squirrel monkeys (A) or common marmosets (B).
Mentions: To compare the functionality of human and New World monkey CD4 molecules in supporting HIV-1 entry, Cf2Th cells expressing either human or New World monkey CD4 in combination with human or New World monkey CXCR4 were exposed to recombinant HIV-1 expressing EGFP, as described above. As was observed previously, cells expressing human CD4 and either SS or CJ CXCR4 proteins supported HIV-1 entry at roughly 50% the level seen for cells expressing human CD4 and human CXCR4 molecules (Fig. 4, A and B) . Cells expressing either SS or CJ CD4 did not support efficient infection regardless of the coexpression of human or New World monkey CXCR4 molecules. A small percentage of EGFP-positive cells was observed after infection of the cells expressing both marmoset receptors exposed to the recombinant KB9 virus (Fig. 4 B). This was consistently higher than the background associated with cells transfected only with the human CD4-expressing plasmid. Recombinant HIV-1 pseudotyped with the VSV G glycoprotein infected all of the cells efficiently (data not shown). These results indicate that the New World monkey CD4 molecules are not efficient HIV-1 receptors.

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