HIV structure and organisation

HIV is classified into the family Retroviridae, subfamily Lentiviridae, and genus Lentivirus [20, 21]. The structure of HIV follows the typical pattern of a complex retrovirus family, comprising a single-stranded, positive-sense ribonucleic acid (RNA) genome of about 9.2 kilobases that encodes structural, enzymatic and accessory proteins. A HIV virion is largely spherical in shape, with a diameter of 100 to 120 nm, and encloses its genome within a fullerene (cone-shaped) capsid core. The virus is enveloped with a lipid bilayer derived from the host cell, thus incorporating proteins found in the host membrane, such as the major histocompatibility (MHC) molecules [22, 23], CD44 and lymphocyte function-associated antigen 1 (LFA-1) [24]. Embedded within this membrane are the viral glycoproteins; the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. Each envelope subunit displays on the virion surface as a trimer of the outer envelope glycoprotein gp120, non-covalently liked to a trimer of gp41, the transmembrane protein that anchors this glycoprotein complex to the surface of the virion. The envelope protein is the most variable component of HIV, although gp120 itself is structurally divided into highly variable (V) and more constant (C) regions. The constant regions of the gp120 envelope are often associated with the “non-neutralising face”, as they are buried within the trimer [25, 26]. In contrast, the variable domains are associated with the “neutralizing face” of the envelope glycoprotein that is exposed to antibodies. Variability of this regions underlies immune escape. The variable domains also give the capacity of the virus to change receptor usage. In particular, the V3 loop of HIV gp120 can change the  ability of the virus to use the HIV co-receptors CXCR4 and CCR5 (receptors for HIV will be covered later in this chapter). Finally, the envelope glycoprotein gp120 has over half of its molecular weight attributed to carbohydrate structures, in the form of complex and high mannose N-linked glycans. These glycans decorate the majority of the exposed outer gp120 surface, which is known as the “silent face” given its ability to protect the envelope from antibody responses [25, 26].

The viral structural proteins are derived from the Gag polyprotein, which is present in approximately 2,400 copies in an immature virion according to current estimates [27]. Viral maturation leads to the cleavage of the Gag polyprotein, giving rise to Matrix (MA; p17) and Capsid (CA; p24) proteins, as well as the smaller peptides Nucleocapsid (NC; p7), p6, p2 and p1 [28].  Matrix associates with the inner membrane of the mature virion, whilst Capsid forms the viral core, enclosing two single strands of viral RNA. The core structure is a cone shape comprised of approximately 1,500 Capsid proteins assembled into hexameric and pentameric rings [29, 30]. Viral proteins found within the capsid core include the NC, which is found associated with the viral RNA, as well as Protease (PR), Integrase (IN) and Reverse Transcriptase (RT) proteins [31].

 The genomic organisation of HIV is extremely efficient. Use of all three reading frames (the triplet codes) of the genetic sequence permits overlapping of gene-coding regions. There are nine genes of HIV. These encode proteins that may be broadly classified into structural, catalytic, regulatory, and accessory classes (Table 1).

 In addition to   the   functions   performed   by   these   proteins in the viral lifecycle, the nucleic acid sequence of the virus possesses intrinsic functions. For example, the Rev responsive element, within the coding region for gp41, interacts with the Rev protein to assist export of spliced RNA transcripts from the nucleus of the cell [32]. The long-terminal repeat (LTR) region has a transcription-promoter function in the integrated deoxyribonucleic acid (DNA) provirus [33] and contains regions essential for reverse transcription, integration into the host-cell genome and genomic RNA dimerization [34].

 Table 1. Summary of HIV-1 gene products and their functions

Viral Gene

Viral Protein

Designation and size (kDa)



Structural Proteins



MA, p17

Targets virion assembly through binding to PI (4,5) P2 domains at the plasma membrane; binds gp41 to incorporate Env in nascent virions



CA, p24

Forms the capsid-rich core via hexameric and pentameric CA structures; mediates Gag oligomerisation and assembly

[29, 30, 39]


NC, p7

Binds viral RNA and packages the genome in the core; mediates Gag oligomerisation and assembly




Promotes membrane fission of nascent virions via PTAP-Tsg101 recruitment of the ESCRT complex; binds Vpr protein and packages it in the core



Surface envelope glycoprotein

SU, gp120

Envelope surface protein; binds to CD4 receptor and chemokine receptors on target cell


Transmembrane envelope glycoprotein

TM, gp41

Envelope transmembrane protein; mediates fusion via 'fusion peptide'

[50, 51]


Reverse Transcriptase

RT, p66, p51

RNA-dependent-DNA-polymerase; converts viral ssRNA to linear DNA

[52, 53]


IN, p32

Facilitates integration of HIV DNA into host genome; involved in dynein-mediated transport of the RTC.



PR, p10

Cleavage of polyprotein components of Gag-Pol

[58, 59]

Regulatory Proteins


Trans-Activator of Transcription

Tat, p14

Activator of transcription of HIV ssRNA; essential for virus replication



Regulator of Virion protein expression

Rev, p19

Post-transcriptional regulation of viral genes, including export of viral RNA from the nucleus

[32, 64]

Accessory Proteins


Negative Regulatory Factor

Nef, p27

Infectivity enhancement; CD4 and MHC class I down-regulation; cellular activation and signaling; Counters the restriction factor SERINC to increase virion infectivity

[65-71] [72]


Viral Protein R

Vpr, p15

Helps in nuclear transport of HIV post entry; induces G2 cell cycle arrest in infected cells



Viral Protein U

Vpu, p16

Enhances the release of virus particles by counter-acting the interferon induced restriction factor Tetherin; promotes CD4 degradation



Virion Infectivity Factor

Vif, p23

Counteracts the anti-viral activity of APOBEC3 protein group. The latter protein group are HIV restriction factors that hypermutate HIV genomes and render them non-functional.