Inhibition of HIV Replication by Host Cellular Factors

complex (RTC). RT has three essential activities for virus replication: RNA-dependent DNA polymerase (i.e. reverse transcriptase), RNase H activity that cleaves the genomic RNA in RNA/ DNA hybrids during cDNA synthesis, and DNA-dependent DNA polymerase activity (for synthesis of the second strand of the proviral DNA). The result is a double-stranded DNA replica of the original genomic RNA. The double-stranded viral DNA, as part of the preintegration complex (PIC), penetrates the host cell nucleus through the pores in the nuclear membrane. Another viral enzyme, integrase, inserts the double-stranded viral DNA in the host cell chromosomal DNA (reviewed in [8]). The PIC is composed of several cellular and viral components, e.g. viral DNA, RT, integrase (IN), capsid (CA), matrix (MA) and Vpr proteins. In activated cells, the proviral DNA is transcribed, acting as a template for mRNA synthesis. The viral mRNA exists as three distinct classes: multiply spliced (~2kb), single-spliced (4-5kb) and unspliced (9kb). The multiply spliced transcripts are the first to accumulate soon after infection and encode the regulatory proteins Tat, Rev and Nef. The accumulation of Rev protein enables the efficient nuclear export of single-spliced and unspliced mRNA and to an increase in the levels of these mRNAs (reviewed in [9]). intracellular pool or by introducing mutations in nascent chain of viral DNA; MxB impairs the nuclear import and/or the integration step; and finally, Tetherin induces virion retention at the host-cell membrane. some inhibition reveals that a functional preintegration complex intermediate can