HIV (Human Immunodeficiency Virus(

 Human immunodeficiency virus (HIV), a causative virus of acquired immune deficiency syndrome ( AIDS), is a member of the Lentivirus genus of the family Retroviridae. The first isolate was reported in 1983 and was named lymphadenopathy-associated virus ) LAV). Other isolates, such as human T-lymphotropic virus type III (HTLV-III) and AIDS-associated retrovirus (ARV), were reported in 1984. These HIV isolates were later categorized as HIV-1, because a serologically unique HIV isolate was discovered in 1986 and designated as HIV-2. Great sequence variation, especially in the env gene, is characteristic of HIV, and at least nine subtypes of HIV-1 (A to I) and/or five of HIV-2 (A to E) have been classified.

 HIV virions are spherical and about 110 nm in diameter. The HIV virion has a lipid-bilayer envelope, and approximately 72 knobs (spikes) protrude from the envelope. Each knob is composed of oligomeric surface protein (SU:gp120 in HIV-1 and gp130 in HIV-2) and transmembrane protein (TM:gp41 in both HIV-1 and HIV-2). Inside the envelope, the capsid proteins (CA:p24) form the bullet-shaped capsid shell. The matrix protein (MA:p17) is present between the envelope and CA. The nucleocapsid protein (NC:p9) binds to the viral genome. SU, TM, MA, CA, and NC are the major structural proteins. Two identical copies of single-stranded RNA of positive polarity are contained in a HIV virion as the genome. The enzymes proteinase (PR), reverse transcriptase (RT) (see Rous Sarcoma Virus (RSV) and Hepatitis B Virus), and integrase (IN) are also contained in the capsid shell.

 The genome RNA of about 9.2 kb is, like cellular messenger RNAs, capped at the 5′ end and tailed by poly(A) at the 3′ end. The genome has short direct repeats (R) and unique sequences at both ends (U5 at the 5′ end and U3 at the 3′ end). These sequences are important to form long terminal repeats (LTRs) during replication. The coding sequences of HIV have three major genes of retroviruses: gag, pol, and env. The gag gene codes for MA, CA, and NC; the pol gene codes for PR, RT, and IN; the env gene codes for SU and TM. It is characteristic of HIV to have accessory genes. Two of them, tat and rev, are essential for replication in both HIV-1 and HIV-2. HIV-1 has vif, vpr, nef, and vpu, while HIV-2 has vif, vpr, nef, and vpx instead of vpu as nonessential accessory genes.

 The replicative cycle starts with an interaction between the virion and the cell surface receptor. The principal receptor for HIV is the CD4 molecule, which is expressed on CD4-positive T lymphocytes, macrophages, and so on. The CD4-binding sites on the virion are on SU (gp120). The next crucial step after binding is fusion of the virion envelope and the plasma membrane. It has been postulated that an N-terminal hydrophobic domain in TM is the actual fusion protein, which needs to be exposed by a conformational change in the envelope glycoproteins caused by SU binding to CD4.

 Interestingly, an additional cell-surface molecule, actually a chemokine receptor like CCR5 or CXCR4, is needed to initiate the fusion process. These chemokine receptors are referred to as “co-receptors” for HIV infection. Once the nucleoproteins get into the cytoplasm, synthesis of the minus-strand DNA starts using RT and host transfer RNA^Lys attached near the 5′ end of the viral genome as a primer. Synthesis of viral DNA is similar to that of other mammalian and avian retroviruses, but lentiviruses, including HIV, start the plus-strand DNA synthesis at two sites; one is a polypurine tract near U3 like many other retroviruses, and the other is a central polypurine tract at the end of pol gene. Double-stranded viral DNA with the LTR on both ends is carried to the nucleus as preintegration complex. Presumably, nuclear localization signals in MA and/or Vpr play an important role in nuclear translocation of the preintegration complex. While mammalian and avian retroviruses require cell division for efficient virus production, HIV can infect nondividing, terminally differentiated cells. Linear double-stranded viral DNA is the substrate for IN and the direct precursor of integrated provirus.

 Integrated proviral DNA has an LTR on both ends. Full-length viral RNA is transcribed from the U3/R boundary in the 5′LTR to the R/U5 boundary in the 3′LTR, and 5′-capped and 3′-poly(A)-tailed viral RNA serves as both genome RNA and mRNA for translation. The mRNA undergoes complex RNA splicing. The env and accessory gene products are translated from spliced mRNAs.

The env gene products (Env) are translated as a precursor protein, gp160, in the rough endoplasmic reticulum, processed to gp120 (SU) and gp41 (TM), and expressed on the cell surface. The gag and pol gene products (Gag and Pol) are translated from unspliced mRNA. The pol gene is not in the same reading frame as gag gene, however, and pol gene products are translated as a Gag–Pol fusion protein by ribosomal frameshifting at the gag–pol boundary. Viral assembly occurs just below the plasma membrane. Virions bud out from the cells, covered by the plasma membrane (viral envelope( with SU and TM. Viral proteinase (PR) digests Gag and Gag–Pol fusion proteins to MA, CA, NC, PR, RT, and IN, and the virions are matured.