Characterization of the Protective HIV-1 CTL Epitopes and the Corresponding HLA Class I Alleles: A Step towards Designing CTL Based HIV-1 Vaccine

Table 1

Function of different HIV proteins.

Protein	Precursor	Functions
P17	Gag	Matrix protein p17 has two main functions. Firstly it targets Gag-pol polyproteins to the plasma membrane by the help of a membrane-binding signal which contains myristoylated N-terminus. Secondly it plays an essential role in the nuclear localization of the viral genome.
P24	Gag	Protein p24 forms the nucleocapsid that encapsulates the viral genomic RNA in the virion. The core is disassembled immediately after the entry of virion into host cell.
P7	Gag	Nucleocapsid protein p7 encapsulates viral genomic RNA and hence provides protection to viral genome. It binds these RNAs through its zinc finger motifs. It also acts as a nucleic acid chaperone as it tends to facilitate the rearrangement of nucleic acid secondary structure during reverse transcription of genomic RNA.
RT	Gag-pol	Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that facilitates the reverse transcription of viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme also displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes.
Integrase	Gag-pol	Integrase catalyzes integration of viral DNA into the host chromosome, by a multistep process involving DNA cutting and joining reactions.
Protease	Gag-pol	Cleavage of viral precursor polyproteins into mature proteins
Gp120	GP160	The surface protein gp120 (SU) facilitates the anchoring of the virus to the host target cell (CD4+) by binding to the primary receptor CD4. This interaction induces a change in the conformation exposing a high affinity binding site for a chemokine coreceptor (CXCR4 and/or CCR5) and promotes subsequent interaction between the envelope protein and CXCR4 and/or CCR5.
Tat		Tat acts as a nuclear transcriptional activator of viral gene expression that is essential for viral transcription from the LTR promoter. It also directs the components of the cellular transcription machinery into the viral RNA to promote transcription by the RNA polymerase complex.
Vif		It ensures the downregulation of APOBEC3G by recruiting the ubiquitin-proteasome machinery that targets APOBEC3G for degradation. It also binds to viral RNA and affects the stability of viral nucleoprotein core.
Vpr		It is largely involved in the transport of the viral preintegration (PIC) complex to the nucleus during the early phase of the infection. It probably interacts with karyopherin alpha/KPNA1 and KPNA2 thereby increasing their affinity for basic-type nuclear localization signal harboring proteins such as viral matrix protein, thus facilitating the translocation of the viral proteins into the nucleus.
Vpu		It promotes virion budding, by targeting human CD4 and CD317 to proteasomal degradation. CD4 degradation hinders any possible interactions between viral Env and human CD4 in the endoplasmic reticulum. It helps the proper Env assembly into virions.
Nef		(1) Downregulation of surface MHC-I molecules.; (2) Downregulation of cell surface CD4 antigen. It interacts with the Src family kinase LCK and induces LCK-CD4 dissociation. Subsequently it causes clathrin-dependent endocytosis of CD4 antigen. Ultimately, the CD4 are decreased and infected cells.; (3) It decreases the number of viral receptors and hence prevents reinfection by more HIV particles.; (4) It prevents the apoptosis of the infected cell by inhibiting the Fas and TNFR-mediated death signals. It also interacts with p53 and protects the infected cell against p53-mediated apoptosis. Furthermore, it regulates the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that induces phosphorylation of Bad.