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Cyclophilin A interacts with diverse lentiviral capsids.

Lin TY, Emerman M - Retrovirology (2006)

Bottom Line: This binding positively affects some early stage of the viral life-cycle because prevention of binding either by drugs that occupy that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks down intracellular CypA level diminishes viral infectivity.We find that diverse lentiviruses, FIV and SIVagmTAN also bind to CypA.Mutagenesis of FIV CA showed that an amino acid that is in a homologous position to the proline at amino acid 90 of HIV-1 CA is essential for FIV interactions with CypA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pathobiology Graduate Program, University of Washington, Seattle, WA 98195, USA. linty@u.washington.edu

ABSTRACT

Background: The capsid (CA) protein of HIV-1 binds with high affinity to the host protein cyclophilin A (CypA). This binding positively affects some early stage of the viral life-cycle because prevention of binding either by drugs that occupy that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks down intracellular CypA level diminishes viral infectivity. The closely related lentivirus, SIVcpz also binds CypA, but it was thought that this interaction was limited to the HIV-1/SIVcpz lineage because other retroviruses failed to interact with CypA in a yeast two-hybrid assay.

Results: We find that diverse lentiviruses, FIV and SIVagmTAN also bind to CypA. Mutagenesis of FIV CA showed that an amino acid that is in a homologous position to the proline at amino acid 90 of HIV-1 CA is essential for FIV interactions with CypA.

Conclusion: These results demonstrate that CypA binding to lentiviruses is more widespread than previously thought and suggest that this interaction is evolutionarily important for lentiviral infection.

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CypA/CA interaction in SIVmac, HIV-1, and SIVagmTAN. (A) Sequence alignment of HIV-1 and other lentiviruses. The amino acid sequences of the loop between α helices 4 and 5 were aligned with HIV-1. Prolines are in bold, and gaps are indicated as "-". (B) Infectivity of HIV-1, SIVmac, and SIVagmTAN under the TrimCyp restriction. CRFK or CRFK-TrimCyp cells were infected with HIV-1-luc, SIVmac-luc, and SIVagmTan-luc, and the infectivity was determined by luminometer.
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Figure 5: CypA/CA interaction in SIVmac, HIV-1, and SIVagmTAN. (A) Sequence alignment of HIV-1 and other lentiviruses. The amino acid sequences of the loop between α helices 4 and 5 were aligned with HIV-1. Prolines are in bold, and gaps are indicated as "-". (B) Infectivity of HIV-1, SIVmac, and SIVagmTAN under the TrimCyp restriction. CRFK or CRFK-TrimCyp cells were infected with HIV-1-luc, SIVmac-luc, and SIVagmTan-luc, and the infectivity was determined by luminometer.

Mentions: We aligned the amino acids in the region between the prediced alpha-helices 4 and 5 of CA from a number of different lentiviruses, and noticed that SIVagmTAN, similar to FIV, has 5 prolines, and that the length of the SIVagmTAN loop (9 amino acids) is the same as HIV-1 (Fig. 5A). We therefore tested whether SIVagmTAN also interacts with CypA using the TrimCyp assay (Fig. 5B). Consistent with other reports [5,6], SIVmac, as a negative control, is not sensitive to the TrimCyp. On the other hand, SIVagmTAN behaves like HIV-1 and FIV. The infectivity of SIVagmTAN is strongly restricted by TrimCyp protein, and the restriction can be counteracted by the treatment of CsA (Fig. 5B). This result suggests that the CA of SIVagmTAN is also recognized by the CypA, and that the ability of CypA to recognize lentiviral capsids is widespread, although not universal, among lentiviruses.


Cyclophilin A interacts with diverse lentiviral capsids.

Lin TY, Emerman M - Retrovirology (2006)

CypA/CA interaction in SIVmac, HIV-1, and SIVagmTAN. (A) Sequence alignment of HIV-1 and other lentiviruses. The amino acid sequences of the loop between α helices 4 and 5 were aligned with HIV-1. Prolines are in bold, and gaps are indicated as "-". (B) Infectivity of HIV-1, SIVmac, and SIVagmTAN under the TrimCyp restriction. CRFK or CRFK-TrimCyp cells were infected with HIV-1-luc, SIVmac-luc, and SIVagmTan-luc, and the infectivity was determined by luminometer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1622752&req=5

Figure 5: CypA/CA interaction in SIVmac, HIV-1, and SIVagmTAN. (A) Sequence alignment of HIV-1 and other lentiviruses. The amino acid sequences of the loop between α helices 4 and 5 were aligned with HIV-1. Prolines are in bold, and gaps are indicated as "-". (B) Infectivity of HIV-1, SIVmac, and SIVagmTAN under the TrimCyp restriction. CRFK or CRFK-TrimCyp cells were infected with HIV-1-luc, SIVmac-luc, and SIVagmTan-luc, and the infectivity was determined by luminometer.
Mentions: We aligned the amino acids in the region between the prediced alpha-helices 4 and 5 of CA from a number of different lentiviruses, and noticed that SIVagmTAN, similar to FIV, has 5 prolines, and that the length of the SIVagmTAN loop (9 amino acids) is the same as HIV-1 (Fig. 5A). We therefore tested whether SIVagmTAN also interacts with CypA using the TrimCyp assay (Fig. 5B). Consistent with other reports [5,6], SIVmac, as a negative control, is not sensitive to the TrimCyp. On the other hand, SIVagmTAN behaves like HIV-1 and FIV. The infectivity of SIVagmTAN is strongly restricted by TrimCyp protein, and the restriction can be counteracted by the treatment of CsA (Fig. 5B). This result suggests that the CA of SIVagmTAN is also recognized by the CypA, and that the ability of CypA to recognize lentiviral capsids is widespread, although not universal, among lentiviruses.

Bottom Line: This binding positively affects some early stage of the viral life-cycle because prevention of binding either by drugs that occupy that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks down intracellular CypA level diminishes viral infectivity.We find that diverse lentiviruses, FIV and SIVagmTAN also bind to CypA.Mutagenesis of FIV CA showed that an amino acid that is in a homologous position to the proline at amino acid 90 of HIV-1 CA is essential for FIV interactions with CypA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pathobiology Graduate Program, University of Washington, Seattle, WA 98195, USA. linty@u.washington.edu

ABSTRACT

Background: The capsid (CA) protein of HIV-1 binds with high affinity to the host protein cyclophilin A (CypA). This binding positively affects some early stage of the viral life-cycle because prevention of binding either by drugs that occupy that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks down intracellular CypA level diminishes viral infectivity. The closely related lentivirus, SIVcpz also binds CypA, but it was thought that this interaction was limited to the HIV-1/SIVcpz lineage because other retroviruses failed to interact with CypA in a yeast two-hybrid assay.

Results: We find that diverse lentiviruses, FIV and SIVagmTAN also bind to CypA. Mutagenesis of FIV CA showed that an amino acid that is in a homologous position to the proline at amino acid 90 of HIV-1 CA is essential for FIV interactions with CypA.

Conclusion: These results demonstrate that CypA binding to lentiviruses is more widespread than previously thought and suggest that this interaction is evolutionarily important for lentiviral infection.

Show MeSH
Related in: MedlinePlus