Abstract
BackgroundIsolation of novel retroviral restriction factors will open new avenues for anti-HIV/AIDS treatment. Although HIV-1 replication is restricted by APOBEC3G/APOBEC3F, TRIM5α, and CD317, none defend HIV-1 infection under natural conditions. Previously, we demonstrated a host factor from the human T cell line CEM.NKR that potently restricted wild-type HIV-1 replication. Interestingly, this restriction resembled the APOBEC3G/APOBEC3F pattern in that viral replication was inhibited from the second round of replication cycle at a post-entry step.ResultsHere, we further characterized this factor and found it distinguishable from the known anti-HIV APOBEC3 proteins. Although CEM.NKR cells expressed both APOBEC3G and APOBEC3F, their levels were at least 10 or 4-fold lower than those in H9 cells, and importantly, Vif effectively neutralized their activity. Among eight subclones isolated from CEM.NKR cells, one was relatively permissive, four were semi-permissive, and three were completely non-permissive for HIV-1 replication. When the levels of APOBEC3 expression were determined, all these clones retained similar low levels of APOBEC3DE, APOBEC3F, APOBEC3G and APOBEC3H expression, and no APOBEC3B expression was detected. Since the vif from SIVmac can effectively neutralize APOBEC3B and APOBEC3H, recombinant HIV-1 expressing this SIV gene were created. However, these viruses still failed to replicate in CEM.NKR cells. We also confirmed that HIV-1 restriction in CEM.NKR was not due to a loss of calnexin expression.ConclusionTaken together, these results not only demonstrate that all these aforementioned anti-HIV APOBEC3 proteins do not contribute to this HIV-1 restriction, but also shed light on a novel and potent HIV-1 inhibitor in CEM.NKR cells.
Highlights
Isolation of novel retroviral restriction factors will open new avenues for anti-HIV/AIDS treatment
Taken together, these results demonstrate that all these aforementioned anti-HIV APOBEC3 proteins do not contribute to this HIV-1 restriction, and shed light on a novel and potent HIV-1 inhibitor in CEM.NKR cells
H9 cells alone were productively infected with peak viral production at ~500 ng/ml p24Gag, whereas CEM.NKR cells alone were poorly infected with maximal viral production at ~5 ng/ml p24Gag (Fig. 1A)
Summary
Isolation of novel retroviral restriction factors will open new avenues for anti-HIV/AIDS treatment. We demonstrated a host factor from the human T cell line CEM.NKR that potently restricted wild-type HIV-1 replication. This restriction resembled the APOBEC3G/APOBEC3F pattern in that viral replication was inhibited from the second round of replication cycle at a post-entry step. CEM is a human T lymphosarcoma cell line isolated from an infant female patient with acute leukemia [1]. This human T cell line has been useful in HIV research because of its infectability and has significantly contributed to our understanding of innate intracellular immunity to retroviruses. Both CEM-SS and CEM-T4 are permissive for vifPage 1 of 12
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