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CXCR4/fusin is not a species-specific barrier in murine cells for HIV-1 entry.

Tachibana K, Nakajima T, Sato A, Igarashi K, Shida H, Iizasa H, Yoshida N, Yoshie O, Kishimoto T, Nagasawa T - J. Exp. Med. (1997)

Bottom Line: Recently, CXCR4 was shown to function as a coreceptor for T cell line-tropic HIV-1 entry.Here we demonstrated that cells expressing murine CXCR4 and human CD4 fused with cells expressing the env proteins derived from T cell line-tropic HIV-1 and were infected with T cell line-tropic HIV-1 strains.We conclude that murine CXCR4 is not a species specific barrier to the entry of T cell line-tropic HIV-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 590-02, Japan.

ABSTRACT
Since some murine cells expressing human CD4 fail to internalize HIV-1, another block was thought to be located at the level of viral entry in addition to CD4. Recently, CXCR4 was shown to function as a coreceptor for T cell line-tropic HIV-1 entry. Here we demonstrated that cells expressing murine CXCR4 and human CD4 fused with cells expressing the env proteins derived from T cell line-tropic HIV-1 and were infected with T cell line-tropic HIV-1 strains. In contrast, the same cells were not infected with chimeric clones constructed by substitution of monocyte- or macrophage-tropic strain-derived env region or V3 region into T cell line-tropic HIV-1, indicating V3 loop of envelope protein is required for murine CXCR4mediated HIV-1 entry. We conclude that murine CXCR4 is not a species specific barrier to the entry of T cell line-tropic HIV-1.

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The V3 loop of envelope gp120 is required for murine CXCR4-mediated HIV-1  entry. (A) Structure of chimeric  proviral clones. The env protein  or V3 loop region of macrophage-tropic HIV-1 strain SF162  was introduced into a T cell linetropic strain NL432 proviral  DNA. E, EcoRI; Ba, BamHI; St,  StuI; Nh, NheI. (B) SW480 cells  expressing human CD4 and  listed chemokine receptors were  infected with the chimeric  proviral clones, NL432env-162 or  NL432v3-162.
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Figure 3: The V3 loop of envelope gp120 is required for murine CXCR4-mediated HIV-1 entry. (A) Structure of chimeric proviral clones. The env protein or V3 loop region of macrophage-tropic HIV-1 strain SF162 was introduced into a T cell linetropic strain NL432 proviral DNA. E, EcoRI; Ba, BamHI; St, StuI; Nh, NheI. (B) SW480 cells expressing human CD4 and listed chemokine receptors were infected with the chimeric proviral clones, NL432env-162 or NL432v3-162.

Mentions: Human CXCR4-mediated HIV-1 entry has been shown to be inhibited by the monoclonal antibody directed against the V3 loop (6). Then, to confirm that the function of murine CXCR4 can replace the function of human CXCR4 further, we investigated whether the V3 loop of envelope gp120 is required for murine CXCR4-mediated HIV-1 entry. SW480 cells expressing human CD4 and chemokine receptors were infected with viral chimeric clones, NL432env-162 and NL432V3-162. As shown in Fig. 3 A, NL432env-162 was constructed by substitution of an M-tropic strain SF162 env region into a T-tropic strain NL432 proviral clone. NL432V3-162 was constructed by substitution of an SF162 V3 region into a NL432 proviral clone. Although NL432 entered SW480 cells expressing murine CXCR4 and human CD4, both NL432env-162 and NL432V3-162 failed to enter those cells. Both NL432env-162 and NL432V3-162 entered SW480 cells expressing human CCR5 and human CD4. These results revealed that the V3 region is required for viral entry supported by murine CXCR4 as well as human CXCR4.


CXCR4/fusin is not a species-specific barrier in murine cells for HIV-1 entry.

Tachibana K, Nakajima T, Sato A, Igarashi K, Shida H, Iizasa H, Yoshida N, Yoshie O, Kishimoto T, Nagasawa T - J. Exp. Med. (1997)

The V3 loop of envelope gp120 is required for murine CXCR4-mediated HIV-1  entry. (A) Structure of chimeric  proviral clones. The env protein  or V3 loop region of macrophage-tropic HIV-1 strain SF162  was introduced into a T cell linetropic strain NL432 proviral  DNA. E, EcoRI; Ba, BamHI; St,  StuI; Nh, NheI. (B) SW480 cells  expressing human CD4 and  listed chemokine receptors were  infected with the chimeric  proviral clones, NL432env-162 or  NL432v3-162.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196327&req=5

Figure 3: The V3 loop of envelope gp120 is required for murine CXCR4-mediated HIV-1 entry. (A) Structure of chimeric proviral clones. The env protein or V3 loop region of macrophage-tropic HIV-1 strain SF162 was introduced into a T cell linetropic strain NL432 proviral DNA. E, EcoRI; Ba, BamHI; St, StuI; Nh, NheI. (B) SW480 cells expressing human CD4 and listed chemokine receptors were infected with the chimeric proviral clones, NL432env-162 or NL432v3-162.
Mentions: Human CXCR4-mediated HIV-1 entry has been shown to be inhibited by the monoclonal antibody directed against the V3 loop (6). Then, to confirm that the function of murine CXCR4 can replace the function of human CXCR4 further, we investigated whether the V3 loop of envelope gp120 is required for murine CXCR4-mediated HIV-1 entry. SW480 cells expressing human CD4 and chemokine receptors were infected with viral chimeric clones, NL432env-162 and NL432V3-162. As shown in Fig. 3 A, NL432env-162 was constructed by substitution of an M-tropic strain SF162 env region into a T-tropic strain NL432 proviral clone. NL432V3-162 was constructed by substitution of an SF162 V3 region into a NL432 proviral clone. Although NL432 entered SW480 cells expressing murine CXCR4 and human CD4, both NL432env-162 and NL432V3-162 failed to enter those cells. Both NL432env-162 and NL432V3-162 entered SW480 cells expressing human CCR5 and human CD4. These results revealed that the V3 region is required for viral entry supported by murine CXCR4 as well as human CXCR4.

Bottom Line: Recently, CXCR4 was shown to function as a coreceptor for T cell line-tropic HIV-1 entry.Here we demonstrated that cells expressing murine CXCR4 and human CD4 fused with cells expressing the env proteins derived from T cell line-tropic HIV-1 and were infected with T cell line-tropic HIV-1 strains.We conclude that murine CXCR4 is not a species specific barrier to the entry of T cell line-tropic HIV-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 590-02, Japan.

ABSTRACT
Since some murine cells expressing human CD4 fail to internalize HIV-1, another block was thought to be located at the level of viral entry in addition to CD4. Recently, CXCR4 was shown to function as a coreceptor for T cell line-tropic HIV-1 entry. Here we demonstrated that cells expressing murine CXCR4 and human CD4 fused with cells expressing the env proteins derived from T cell line-tropic HIV-1 and were infected with T cell line-tropic HIV-1 strains. In contrast, the same cells were not infected with chimeric clones constructed by substitution of monocyte- or macrophage-tropic strain-derived env region or V3 region into T cell line-tropic HIV-1, indicating V3 loop of envelope protein is required for murine CXCR4mediated HIV-1 entry. We conclude that murine CXCR4 is not a species specific barrier to the entry of T cell line-tropic HIV-1.

Show MeSH
Related in: MedlinePlus