1. Adsorption. The HIV envelope gp120 must attach to both a CD4 molecule and a chemokine receptor on the surface of such cells as macrophages and T4-helper lymphocytes in order to enter the cell. The gp120 first binds to a CD4 molecule on the plasma membrane of the host cell. The interaction between the gp120 and the CD4 molecule on the host cell induces a change in shape that brings the chemokine receptor binding domains of the gp120 into proximity with the host cell chemokine receptor.

2. Penetration. The binding of a portion or domain of the HIV surface glycoprotein gp120 to a CD4
molecule on the host cell induces a change in shape that brings the chemokine receptor binding domains of the gp120 into proximity with the host cell chemokine receptor. This, in turn, brings about a conformational change that exposes a previously buried portion of the transmembrane glycoprotein gp41 enabling the
viral envelope to fuse with the host cell membrane. After fusion of the viral envelope with the host cell cytoplasmic membrane, the genome-containing protein core of the virus enters the host cell's cytoplasm.

3. Uncoating and Production of a Provirus. The single-stranded RNA genomes are released from the capsid. HIV uses the enzyme reverse transcriptase to transcribe its RNA genome into single-stranded DNA. As the DNA is being made, the RNA genome is degraded by an RNase. The reverse transcriptase then synthesizes a complementary DNA strand to produce a double-stranded DNA intermediate that enters the infected host cell's nucleus. An HIV enzyme called integrase is used to insert the HIV double-stranded DNA intermediate into the DNA of a host cell's chromosome. HIV is now a provirus.

4. Translation of HIV mRNA. Once synthesized, HIV mRNA goes through the nuclear pores into the rough endoplasmic reticulum to the host cell's ribosomes where it is translated into HIV structural proteins, enzymes, glycoproteins, and regulatory proteins.

A 9 kilobase mRNA is formed that is used for three viral functions:

a. Synthesis of Gag polyproteins (p55). These polyproteins will eventually be cleaved by HIV proteases to become HIV matrix proteins (MA; p17), capsid proteins (CA; p24), and nucleocapsid proteins (NC, p7).
b. Synthesis of Gag-Pol polyproteins (p160). These polyproteins will eventually be cleaved by HIV proteases to become HIV matrix proteins (MA; p17), capsid proteins (CA; p24), proteinase molecules (protease or PR; p10), reverse transcriptase molecules (RT; p66/p51), and integrase molecules (IN; p32).
c. During maturation, these RNA molecules also become the genomes of new HIV virions.

The 9kb mRNA can also be spliced to form a 4kb mRNA and a 2kb mRNA.

The 4kb mRNA is used to:

a. Synthesize the Env polyproteins (gp160). These polyproteins will eventually be cleaved by proteases to become HIV envelope glycoproteins gp120 and gp41.
b. Synthesize 3 regulatory proteins called vif, vpr, and vpu (not shown here).

The 2kb mRNA is used to synthesize 3 regulatory proteins known as tat, rev, and naf (not shown here).

5. Maturation of Envelope Glycoproteins. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi complex where it is cleaved by a protease (proteinase) and processed into the two HIV envelope glycoproteins gp41 and gp120. These are transported to the plasma membrane of the host cell where gp41 anchors the gp120 to the membrane of the infected cell.

6. Maturation and Release. Maturation either occurs in the forming bud or in the immature virion after it buds from the host cell. During maturation, HIV proteases (proteinases) will cleave the polyproteins into individual functional HIV proteins and enzymes.