Transdominant TAT variants of the human immunodeficiency virus

Details Transdominant TAT variants of the human immunodeficiency virus Transdominant TAT variants of the human immunodeficiency virus

1998-06-12

2001-09-04

Scheiner, Laurie (Department: 1648)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Virus or component thereof

C530S300000, C424S188100, C435S069100

Reexamination Certificate

active

06284252

ABSTRACT:

The subject of the present invention is new variants of the TAT protein of the human immunodeficiency virus (HIV), as well as the DNA fragments encoding said variants, the expression cassettes which permit their expression by the recombinant route and the cells containing said expression cassettes. The TAT protein variants, the cassettes and the cells are especially useful for the prevention or treatment of HIV infections.
Acquired immunodeficiency syndrome (AIDS) develops following infection of the T4 lymphocytes of an individual by the HIV virus. The infection may be asymptomatic for many years, but as soon as the cells are activated, the HIV virus replicates rapidly and destroys them. AIDS is characterized by a deficiency of the cellular immunity which has the effect of making the individual particularly sensitive to any opportunistic infection. In July 1992, WHO recorded 501,272 AIDS cases worldwide. (AIDS Information international literature on acquired immunodeficiency syndrome and related retroviruses, 1992, 8, Leeds University Press, Editor A. W. Boylston, Leeds). But these figures are however lower than the reality since this disease constitutes a real epidemic in certain African countries.
AIDS remains a disease whose mortality rate was still very high in 1992. indeed, 90% of people die within the two years following the onset of AIDS. Up until now, no treatment has proved to be totally satisfactory in spite of the many efforts invested. The development of effective treatments has been hampered by the specific complexity of the HIV virus.
HIV is a retrovirus which belongs to the family of lentiviruses. Like any retrovirus, HIV in formed of an envelope surrounding a capsid of protein nature, which contains the genetic material consisting of an RNA molecule associated with various viral proteins which are necessary for the first stages of the replicative cycle.
After infection of a T lymphocyte, the RNA molecule is copied by the viral reverse transcriptase into DNA. The DNA is integrated into the cellular genome and constitutes what is commonly called a provirus. The proviral DNA can stay there in the latent state or can be transcribed into RNA by the cellular machinery to produce on the one hand viral genomic RNA and on the other hand messenger RNAs (mRNA) which will be translated into viral proteins.
The formation of new viral particles or virions occurs by encapsulation of the viral genomic RNA into the capsid. The particle thus formed is detached from the cell by budding taking along a portion of the cellular membrane, into which the viral envelope glycoprotein is incorporated. The virions thus liberated are capable of infecting other lymphoid cells by virtue of a specific and mutual recognition of the CD
4
receptor expressed at the surface of the T4 lymphocytes and of the HIV envelope protein.


REFERENCES:
Green et al., 1989, Cell 58: 215-23.*
Arya, S., 1993, Aids Res. Hum. Retro. 9:839-48.*
Pearson et al., 1990, PNAS, USA 87:5079-83.

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