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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 CCR5-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CCR5, or with New World monkey CD4 and either human or New World monkey CCR5. Recombinant, EGFP-expressing HIV-1 bearing the indicated CCR5-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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fig5: Ability of New World monkey CD4 to support entry of CCR5-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CCR5, or with New World monkey CD4 and either human or New World monkey CCR5. Recombinant, EGFP-expressing HIV-1 bearing the indicated CCR5-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: Studies similar to those described above were performed with cells transiently expressing human or New World monkey CD4 and CCR5 molecules. The results in Fig. 5 confirm that neither New World monkey CD4 nor CCR5 efficiently support the entry of viruses with R5 HIV-1 envelope glycoproteins.


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 CCR5-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CCR5, or with New World monkey CD4 and either human or New World monkey CCR5. Recombinant, EGFP-expressing HIV-1 bearing the indicated CCR5-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

fig5: Ability of New World monkey CD4 to support entry of CCR5-using HIV-1. Cf2Th cells were cotransfected with human CD4 and either human or New World monkey CCR5, or with New World monkey CD4 and either human or New World monkey CCR5. Recombinant, EGFP-expressing HIV-1 bearing the indicated CCR5-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: Studies similar to those described above were performed with cells transiently expressing human or New World monkey CD4 and CCR5 molecules. The results in Fig. 5 confirm that neither New World monkey CD4 nor CCR5 efficiently support the entry of viruses with R5 HIV-1 envelope glycoproteins.

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