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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 chemokine receptors to support HIV-1 entry. Cf2Th cells were cotransfected with (A) human CD4 and human, squirrel monkey, or common marmoset CXCR4, or (B) human CD4 and human, squirrel monkey, or common marmoset CCR5. Recombinant HIV-1 containing the indicated HIV-1 envelope glycoproteins and encoding EGFP was incubated with the cells. 48 h later, EGFP-positive cells were scored. To control for variation in transfection efficiency, the values shown were normalized based on CD4 expression levels determined by Q4120 antibody staining of cell cultures plated in parallel. The entry levels observed in cells expressing human CXCR4 (A) or CCR5 (B) were used as a baseline and all other entry values were multiplied by the percent that their associated CD4 expression level differed from the CD4 expression levels of the reference cells. In the cases where little or no infection was seen, the value is indicated numerically.
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fig3: Ability of New World monkey chemokine receptors to support HIV-1 entry. Cf2Th cells were cotransfected with (A) human CD4 and human, squirrel monkey, or common marmoset CXCR4, or (B) human CD4 and human, squirrel monkey, or common marmoset CCR5. Recombinant HIV-1 containing the indicated HIV-1 envelope glycoproteins and encoding EGFP was incubated with the cells. 48 h later, EGFP-positive cells were scored. To control for variation in transfection efficiency, the values shown were normalized based on CD4 expression levels determined by Q4120 antibody staining of cell cultures plated in parallel. The entry levels observed in cells expressing human CXCR4 (A) or CCR5 (B) were used as a baseline and all other entry values were multiplied by the percent that their associated CD4 expression level differed from the CD4 expression levels of the reference cells. In the cases where little or no infection was seen, the value is indicated numerically.

Mentions: To determine the ability of the New World monkey chemokine receptors to support HIV-1 infection, Cf2Th canine thymocytes transiently expressing human CD4 and either human, SS or CJ chemokine receptors were exposed to recombinant HIV-1 bearing different HIV-1 envelope glycoproteins. The ability of the SS and CJ CXCR4 and CCR5 proteins to allow HIV-1 infection, relative to that of the human receptors, was assessed by monitoring the expression of EGFP, which is encoded by the recombinant virus, in the target cells. Fig. 3 A shows that the squirrel monkey and common marmoset CXCR4 molecules support the entry of viruses bearing several X4 or R5X4 HIV-1 envelope glycoproteins, with an efficiency roughly 50% of that seen for human CXCR4. The different infection efficiencies associated with cells expressing human CXCR4 may relate to intrinsic differences in the efficiencies of the particular HIV-1 envelope glycoproteins and/or factors associated with individual preparations of each of the viral stocks.


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 chemokine receptors to support HIV-1 entry. Cf2Th cells were cotransfected with (A) human CD4 and human, squirrel monkey, or common marmoset CXCR4, or (B) human CD4 and human, squirrel monkey, or common marmoset CCR5. Recombinant HIV-1 containing the indicated HIV-1 envelope glycoproteins and encoding EGFP was incubated with the cells. 48 h later, EGFP-positive cells were scored. To control for variation in transfection efficiency, the values shown were normalized based on CD4 expression levels determined by Q4120 antibody staining of cell cultures plated in parallel. The entry levels observed in cells expressing human CXCR4 (A) or CCR5 (B) were used as a baseline and all other entry values were multiplied by the percent that their associated CD4 expression level differed from the CD4 expression levels of the reference cells. In the cases where little or no infection was seen, the value is indicated numerically.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196058&req=5

fig3: Ability of New World monkey chemokine receptors to support HIV-1 entry. Cf2Th cells were cotransfected with (A) human CD4 and human, squirrel monkey, or common marmoset CXCR4, or (B) human CD4 and human, squirrel monkey, or common marmoset CCR5. Recombinant HIV-1 containing the indicated HIV-1 envelope glycoproteins and encoding EGFP was incubated with the cells. 48 h later, EGFP-positive cells were scored. To control for variation in transfection efficiency, the values shown were normalized based on CD4 expression levels determined by Q4120 antibody staining of cell cultures plated in parallel. The entry levels observed in cells expressing human CXCR4 (A) or CCR5 (B) were used as a baseline and all other entry values were multiplied by the percent that their associated CD4 expression level differed from the CD4 expression levels of the reference cells. In the cases where little or no infection was seen, the value is indicated numerically.
Mentions: To determine the ability of the New World monkey chemokine receptors to support HIV-1 infection, Cf2Th canine thymocytes transiently expressing human CD4 and either human, SS or CJ chemokine receptors were exposed to recombinant HIV-1 bearing different HIV-1 envelope glycoproteins. The ability of the SS and CJ CXCR4 and CCR5 proteins to allow HIV-1 infection, relative to that of the human receptors, was assessed by monitoring the expression of EGFP, which is encoded by the recombinant virus, in the target cells. Fig. 3 A shows that the squirrel monkey and common marmoset CXCR4 molecules support the entry of viruses bearing several X4 or R5X4 HIV-1 envelope glycoproteins, with an efficiency roughly 50% of that seen for human CXCR4. The different infection efficiencies associated with cells expressing human CXCR4 may relate to intrinsic differences in the efficiencies of the particular HIV-1 envelope glycoproteins and/or factors associated with individual preparations of each of the viral stocks.

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