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].

Table3. Functions of known lentiviral proteome [18].
Classification Gene Encoding proteins and functions
Structural proteins env gp120, surface envelope protein SU; gp41, transmembrane envelope protein TM
gag p24, capsid protein CA; p17, matrix protein MA; p9, capsid protein NC
Enzymes pol Reverse transcriptase RT, 66kD; Integrase IN, 32kD
pro Protease PR; dUTPase DU
Gene regulatory proteins tat HIV transactivator, positive regulator of transcription
rev Regulator of virion proteins expression, essential for major viral proteins synthesis and viral replication
Accessory proteins vif Viral infectivity, required for infectivity in some cell types
vpr Virus protein R, nuclear import of pre-integration complex and host cell cycle arrest
vpu Virus protein U, proteasomal degradation of CD44 and release of virions from infected cells
nef Negative factor, role in apoptosis and key in increasing virus infectivity
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