RESUMO
Human immunodeficiency virus type 1 (HIV-1) needs to overcome cellular counter mechanisms such as to successfully propagate itself. Results of our recent studies show that overexpression of insulin-like growth factor II mRNA binding protein 1 (IMP1) inhibits production of infectious HIV-1 particles through adversely affecting virus maturation. Here, we report that IMP1 interacts with HIV-1 Rev protein and its ectopic expression causes relocation of Rev from the nucleus to the cytoplasm. In accordance with this observation, ectopic expression of IMP1 severely diminishes Rev-dependent expression of CAT enzyme and disturbs HIV-1 RNA expression by causing accumulation of the multiple spliced viral RNA. Results of mutagenesis analysis further reveal that the KH4 domain represents the key element of IMP1 in modulating HIV-1 RNA expression. Taken together, these data suggest, in addition to hampering virus assembly, that IMP1 also has an effect on Rev-dependent viral RNA expression.
Assuntos
HIV-1/genética , RNA Viral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Produtos do Gene rev do Vírus da Imunodeficiência Humana/metabolismo , Linhagem Celular , Cloranfenicol O-Acetiltransferase/metabolismo , Regulação Viral da Expressão Gênica , HIV-1/fisiologia , Humanos , Splicing de RNA , Montagem de VírusRESUMO
Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin) restricts the production of a number of enveloped viruses by blocking virus release from the cell surface. This antiviral activity is counteracted by such viral factors as Vpu of human immunodeficiency virus type 1 (HIV-1). Here, we report that Vpu antagonizes human BST-2 but not BST-2 derived from African green monkeys. The determinants of susceptibility to Vpu map to the transmembrane domain of BST-2. In accordance with this, expression of human BST-2 containing a modified transmembrane domain effectively blocks the replication of wild-type Vpu-expressing HIV-1 in CD4+ T cells. Furthermore, these BST-2 variants, as opposed to wild-type human BST-2, are refractory to Vpu-mediated down-regulation as a result of an attenuated interaction with Vpu. In view of the work by others pointing to a key role of the transmembrane domain of Vpu in promoting virus release, our data suggest that a direct interaction through the transmembrane domain of each of these two proteins is a prerequisite for Vpu to down-modulate BST-2.
