Lentivirus Genome Structure and Virus Assembly

Lentivirus, as represented by HIV-1, is a medium-sized (80-100nm) and enveloped, slightly pleomorphic, spherical virus with an isometric nucleocapsid (Figure1A). Unlike other retroviruses, HIV-1 is featured by a set of additional regulatory and accessory genes [11,12]. Its DNA genome, transcribed from HIV-1 ssRNA, is approximately 9.7 kb and contains 9 ORFs. Besides gag, pol, and env (typical of all retroviruses), there are two regulatory (tat and rev) and four accessory (vif, vpr, vpu, and nef) genes specific for HIV-1 (Table 3) as well. All of these protein-coding regions are flanked by 5’ and 3’ LTRs (LTR, long terminal repeat) which are required for HIV-1 life cycle, such as reverse transcription, integration, and gene expression. HIV-1 gene transcription is a complex process, characterized by its specific pattern of viral gene regulation [13]. Several cis-acting sequences, harbored by the HIV-1 LTR, is required for the initiation of viral RNA expression. More than 30 kinds of RNA are converted from the integrated HIV-1 DNA, falling into three classes mRNA according to the splicing pattern, i.e. unspliced, partially spliced, and multiply spliced RNAs [13-15]. The unspliced transcript (about 9kb) is full-length RNA which needs to be packaged as the viral genome into new viral particle but it also functions as mRNA to produce gag and gag-pol polyproteins. The partially spliced transcripts (about 4kb) encode accessory proteins vif, vpr, vpu, and env structural proteins. The multiply spliced RNAs are predominant following the virus infection, and their encoded proteins, the regulatory proteins tat, rev, and nef are highly produced to increase virus infectivity and regulate transcription [16].