Structural requirements for recognition of the human immunodeficiency virus type 1 core during host restriction in owl monkey cells

Human immunodeficiency virus type 1 (HIV-1) infection of simian cells is restricted at an early postentry step by host factors whose mechanism of action is unclear. These factors target the viral capsid protein (CA) and attenuate reverse transcription, suggesting that they bind to the HIV-1 core and interfere with its uncoating. To identify the relevant binding determinants in the capsid, we tested the capacity of viruses containing Gag cleavage site mutations and amino acid substitutions in CA to inhibit restriction of a wild type HIV-1 reporter virus in owl monkey cells. The results demonstrated that a stable, polymeric capsid and a correctly folded amino-terminal CA subunit interface are essential for saturation of host restriction in target cells by HIV-1 cores. We conclude that the owl monkey cellular restriction machinery recognizes a polymeric array of CA molecules, most likely via direct engagement of the HIV-1 capsid in target cells prior to uncoating. Following cell entry, retrovirus particles release their ribo-nucleoprotein cores containing the viral RNA payload into the host cytoplasm. The capsid plays a key role in early postentry steps, as alterations in its structure result in severe loss of infectivity (6, 30, 39, 43, 49). Biochemical analyses of subviral complexes recovered from human immunodeficiency virus typ