Discovery of Human Immunodeficiency Viruses

	Tweet

The identification of HIV-1 as the causative agent of acquired immunodeficiency syndrome (AIDS) just 3 years after the clinical syndrome initially was described represents a remarkable scientific achievement that had its roots in earlier discoveries of animal and human retroviruses. The selective loss of CD4+ helper T lymphocytes in patients with the disease implicated an agent with T-lymphocyte cell tropism. As expected for an etiologic agent, HIV-1 was shown to be uniformly present in subjects with AIDS and to reproduce the hallmark of disease, destruction of T lymphocytes, in tissue culture.

General Biologic Properties of HIV-1

Soon after its discovery, HIV-1 was shown to be biologically, structurally, and genetically distinct from human T-lymphotrophic virus I (HTLV-I) and HTLV-II and more like members of the lentivirus subfamily of retroviruses.

Unlike the leukemia viruses, which lead to immortalization of lymphocytes in vitro and in vivo, HIV-1 exhibits pronounced cytopathic properties for lymphocytes, causing syncytia formation and cell death. Morphologically, HIV-1 differs from HTLV-I and other type C oncogenic retroviruses in exhibiting a dense, cylindrical core surrounded by a lipid envelope typical of lentiviruses.

Like all retroviruses, HIV-1 is a single-stranded plus-sense RNA virus. The RNA-dependent DNA polymerase, or reverse transcriptase, is packaged within the virion core and is responsible for replicating the single-stranded RNA genome through a double-stranded DNA intermediate, which in turn serves as the precursor molecule for proviral integration within the host cell genome. The major structural core proteins of HIV-1 are the p24 capsid protein and the p18 matrix protein, as shown. Surrounding the viral core protein structures is a bilayered lipid envelope that is derived from the outer limiting membrane of the host cell as the virus buds from the cell surface during replication. Studding this outer viral membrane are the envelope glycoproteins, gp120 and gp41, which are encoded by viral-specific genes and are responsible for cell attachment and entry.

Features of this lifecycle distinguish retroviruses from all other viruses. The cell-free virion first attaches to the target cell through a specific interaction between the viral envelope and the host cell membrane. The specificity of this interaction between virus and cell has been shown to be due to a high-affinity specific interaction between the viral gp120 envelope glycoprotein and the target cell-associated CD4 molecule. Following virus adsorption, the viral and cellular membranes fuse, resulting in internalization of the nucleoprotein viral complex. Reverse transcription catalyzed by the viral reverse transcriptase generates a double-stranded DNA copy of the viral RNA within the nucleoprotein complex, and this migrates to the nucleus where covalent integration of viral DNA into the host chromosomes leads to formation of the provirus. Subsequent expression of viral DNA is controlled by a combination of viral and host cellular proteins that interact with viral DNA and RNA regulatory elements.

Transcribed viral mRNA is translated into viral proteins, and new virions are assembled at the cell surface where genomic-length viral RNA, reverse transcriptase, structural and regulatory proteins, and envelope glycoproteins are assembled. Because the HIV-1 provirus is covalently integrated within the host cell chromosome, it represents a stable component of the host genome and is replicated and transmitted to daughter cells in synchrony with cellular DNA. Relevant to subsequent discussions of viral pathogenesis, the integrated provirus is thus permanently incorporated into the host cell genome and may remain transcriptionally latent or may exhibit high levels of gene expression with explosive production of progeny virus.

RELATED STORIES:
Has nothing to do with Science   CDC, UNAIDS and WHO deceptive positions   What about Africa ?  Sex has nothing to do with it   No evidence of ‘HIV’ transmission   Sex has nothing to do with ‘AIDS’   HIV Causes AIDS   The Myth of Sexual ‘AIDS’   What to Tell Your Kids About HIV and AIDS   Rheumatologic Disease   Endocrine Disorders   Cardiac Disease   Renal Disease

Comments

[ + Post Your Own ]

Now you're in the public comment zone. What follows is not Armenian Medical Network's stuff; it comes from other people and we don't vouch for it. A reminder: By using this Web site you agree to accept our Terms of Service. Click here to read the Rules of Engagement.

There are no comments for this entry yet. [ + Comment here + ]