Figure 2.

CypA Induces a Direct Antiviral Resistance against a Family of Capsid Mutants in HIV and SIV that Is Conserved in Human and Macaque Cells

(A) 4,132 sequences of HIV-1 capsid available in the Los Alamos National Laboratory database were aligned and six unique pairs of amino acids preceding Glycine 89-Proline 90 were extracted. A histogram of the number of sequences for this pair of amino acids at this position is shown.

(B) Alignment of the CypA-binding loops of HIV-1 WT, HIV-2 WT, HIVac-2 capsids, and the six pairs of amino acids (as in Figure 4A) in HIV-2 ROD9 instead of Proline 86.

(C) GFP expression in MDDCs 48 hr after infection with HIV-2 WT, HIVac-2, and additional HIV-2 mutants (as indicated) in the presence or absence of CsA (2 μM) (n = 4, paired t test, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001; ns, not statistically significant; bar, mean). Virus inoculum volume is indicated.

(D) Alignment of the CypA-binding loops of HIV-1 WT, HIVac-1, HIV-2 WT, HIVac-2, SIVmac239, and SIVmac239 QPAPQQ85IHAGPLPA.

(E) GFP expression in macaque MDDCs 48 hr after infection with SIVmac239 and SIVmac239 QPAPQQ85IHAGPLPA encoding GFP in Nef and pseudotyped with VSV-G and treated or not with CsA (2 μM) or raltegravir (RAL) (20 μM) (n = 4; representative data for one donor are shown).

(F) GFP expression as in Figure 2E (n = 4, paired t test, ^∗∗p < 0.01, ^∗∗∗∗p < 0.0001; ns, not statistically significant; bar, mean). Virus inoculum volume is indicated.

See also Figure S2.