Fresh pathways to follow

Article Abstract:

Antigens, the substances recognized as foreign by the immune system when it mounts its protective response, are important to researchers who develop vaccines. Exogenous antigens (those that enter antigen-presenting cells, or APCs, from the outside) are one type. These do not replicate themselves and are presented by the APC along with class II major histocompatibility (MHC) molecules to CD4-positive helper T cells, a type of white blood cell active in the immune response. Such T cells facilitate the production of antibodies and of a type of cytotoxic T lymphocyte (CTL). A second type of antigen (endogenous) encounters an immune process tailored for agents that are synthesized inside cells, such as viral proteins. These antigens become associated with MHC class I molecules, and this complex primes CD8-positive CTLs. When designing vaccines, the need for the vaccine to activate both class I and class II processing presents a difficult task. Now it appears that the pathways are not as clear-cut as was formerly thought. It appears, for instance, that influenza virus proteins can associate with both class I and class II molecules, and that endogenously synthesized antigens of hepatitis B virus and of HIV (human immunodeficiency virus) viral envelope antigens can associate with class II molecules. A schematic view of the two types of pathways is presented. Better understanding of the processing and compartmentalization of exogenous and endogenous antigens is called for. Routes of penetration of exogenous viruses could be studied in mammalian viruses. Perhaps antigens that remain associated with membranes always are processed via the class II pathway. The possibility of different processing pathways suggests there is hope for development of an HIV vaccine, since previous views were that a vaccine must work against both infected cells and the free virus. If immunogens (substances that trigger immunity) could be made capable of entering either compartment, the immune response would be dramatically heightened. Use of alternative pathways for activating the body's immune response may be quite important for vaccine development. (Consumer Summary produced by Reliance Medical Information, Inc.)

Antiviral agents

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Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues

Article Abstract:

The human immunodeficiency virus type 1 (HIV-1) causes AIDS (acquired immunodeficiency disease syndrome). Two of the genes present in HIV-1 code for two polyproteins, which are further processed by cleavage of a protease, or enzyme, which cleaves proteins. The protease is also coded for by the virus. The polyproteins are cleaved into four proteins, which are involved in the structure of the virus, and into enzymes, which are necessary for replication of the virus. Inactivation of the protease which cleaves the proteins results in immature viruses which cannot cause infection. HIV-1-infected T lymphocytes grown in tissue culture were treated with peptides synthesized in the laboratory to be analogous, or similar, to the HIV-1 protease. The protease was inhibited by the peptides and could not cleave the viral proteins. The infectivity of the virus was greatly inhibited. Peptide analogues against the HIV-1 protease could be developed for use as a therapy for AIDS. Peptide analogues have a low level of toxicity when used in the body and could be given in amounts that would inhibit viral maturation and infectivity. (Consumer Summary produced by Reliance Medical Information, Inc.)

Analysis, AIDS (Disease), AIDS research, Virus inhibitors, Virus-induced enzymes

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Viral envelope fails to deliver?

Article Abstract:

Further questions have been raised about the use of candidate vaccines against the human immunodeficiency virus (HIV), which use recombinant viral gp120 subunits. The viral gp120 is one of two glycoproteins making up the HIV outer envelope, which can target the virus to certain cells. Recombinant gp120 subunits became candidates for vaccine development because of their ability to raise antibodies to neutralize HIV laboratory strains. However primary viruses remain resistant and increased understand of the HIV envelope is required.

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