Fouchier R A, Meyaard L, Brouwer M, Hovenkamp E, Schuitemaker H
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
Virology. 1996 May 1;219(1):87-95. doi: 10.1006/viro.1996.0225.
The emergence of syncytium-inducing (SI) HIV-1 isolates in infected individuals precedes an accelerated CD4+ T cell decline and is associated with high virus load and rapid disease progression. The exact mechanism by which SI HIV-1 variants may cause this enhanced clinical progression is unknown. Here we demonstrate that an SI HIV-1 isolate had a broader tropism for CD4+ T cell clones (TCC) compared to a macrophage-tropic non-syncytium-inducing (NSI) HIV-1 isolate. Whereas the NSI isolate replicated poorly in 6 of 12 TCC and completely failed to replicate in 3 of 12 TCC, the SI isolate replicated efficiently in all 12 TCC tested. Restriction for replication occurred early in the viral replication cycle, before provirus formation. Infection of TCC with the SI but not with the NSI HIV-1 isolate resulted in massive death of T cells, independent of the extent of virus replication and proportion of infected cells. The high cytopathicity and broader tropism of the SI isolate for primary CD4+ T cells may be directly related to the increased rate of CD4 cell decline and rapid disease progression in carriers of SI variants.
在受感染个体中，合胞体诱导型（SI）HIV-1毒株的出现先于CD4+ T细胞加速减少，并与高病毒载量和疾病快速进展相关。SI HIV-1变体导致这种临床进展加速的确切机制尚不清楚。在此，我们证明，与嗜巨噬细胞的非合胞体诱导型（NSI）HIV-1毒株相比，一株SI HIV-1毒株对CD4+ T细胞克隆（TCC）具有更广泛的嗜性。NSI毒株在12个TCC中的6个中复制不佳，在12个TCC中的3个中完全无法复制，而SI毒株在所有12个测试的TCC中均能高效复制。复制限制发生在病毒复制周期的早期，即在原病毒形成之前。用SI HIV-1毒株而非NSI HIV-1毒株感染TCC会导致T细胞大量死亡，这与病毒复制程度和感染细胞比例无关。SI毒株对原代CD4+ T细胞的高细胞致病性和更广泛嗜性可能与SI变体携带者中CD4细胞减少率增加和疾病快速进展直接相关。
