Katana VentraIP

Structure and genome of HIV

The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983.[1][2] "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV."[3] Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.[4][5]

(group-specific antigen) codes for the precursor gag polyprotein which is processed by viral protease during maturation to MA (matrix protein, p17); CA (capsid protein, p24); SP1 (spacer peptide 1, p2); NC (nucleocapsid protein, p7); SP2 (spacer peptide 2, p1) and P6 protein.[31]

gag

codes for viral enzymes reverse transcriptase (RT) and RNase H, integrase (IN), and HIV protease (PR).[29] HIV protease is required to cleave the precursor Gag polyprotein to produce structural proteins, RT is required to transcribe DNA from RNA template, and IN is necessary to integrate the double-stranded viral DNA into the host genome.[27]

pol

(for "envelope") codes for gp160, which is cleaved by a host protease, furin, within the endoplasmic reticulum of the host cell. The post-translational processing produces a surface glycoprotein, gp120 or SU, which attaches to the CD4 receptors present on lymphocytes, and gp41 or TM, which embeds in the viral envelope to enable the virus to attach to and fuse with target cells.[27][31]

env

HIV pol-1 stem loop

pol

RNA secondary structure[edit]

Several conserved secondary structure elements have been identified within the HIV RNA genome. The HIV viral RNA structures regulates the progression of reverse transcription. [33] The 5'UTR structure consists of series of stem-loop structures connected by small linkers.[10] These stem-loops (5' to 3') include the trans-activation region (TAR) element, the 5' polyadenylation signal [poly(A)], the PBS, the DIS, the major SD and the ψ hairpin structure located within the 5' end of the genome and the HIV Rev response element (RRE) within the env gene.[10][34][35] Another RNA structure that has been identified is gag stem loop 3 (GSL3), thought to be involved in viral packaging.[36][37] RNA secondary structures have been proposed to affect the HIV life cycle by altering the function of HIV protease and reverse transcriptase, although not all elements identified have been assigned a function.


An RNA secondary structure determined by SHAPE analysis has shown to contain three stem loops and is located between the HIV protease and reverse transcriptase genes. This cis regulatory RNA has been shown to be conserved throughout the HIV family and is thought to influence the viral life cycle.[38]

V3 loop[edit]

The third variable loop or V3 loop is a part or region of the Human Immunodeficiency Virus. The V3 loop of the viron's envelope glycoprotein, gp120, allows it to infect human immune cells by binding to a cytokine receptor on the target human immune cell, such as a CCR5 cell or CXCR4 cell, depending on the strain of HIV.[39] The envelope glycoprotein (Env) gp 120/41 is essential for HIV-1 entry into cells. Env serves as a molecular target of a medicine treating individuals with HIV-1 infection, and a source of immunogen to develop AIDS vaccine. However, the structure of the functional Env trimer has remained elusive.[40]

HIV/AIDS research

Rfam entry for HIV pol-1 stem loop

3D model of the complete HIV1 virion

Liu J, Wright ER, Winkler H (2010). "3D Visualization of HIV Virions by Cryoelectron Tomography". Cryo-EM, Part C: Analyses, Interpretation, and Case studies. Methods in Enzymology. Vol. 483. pp. 267–90. :10.1016/S0076-6879(10)83014-9. ISBN 9780123849939. PMC 3056484. PMID 20888479.

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