Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1997-03-05
2001-12-18
Scheiner, Laurie (Department: 1648)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C424S188100, C424S208100
Reexamination Certificate
active
06331616
ABSTRACT:
FIELD OF THE INVENTION
This invention concerns a Feline Immunodeficiency Virus molecular clone which is highly infectious in vivo and which produces immunodeficiency in infected subjects.
BACKGROUND OF THE INVENTION
Feline immunodeficiency virus (FIV), a lentivirus of cats, is associated with feline acquired immunodeficiency syndrome (AIDS). See N. Pedersen et al.,
Science
235: 790 (1987). Disorders associated with FIV infection include chronic gingivitis/stomatitis, chronic upper respiratory infections, chronic enteritis, and recurrent ocular disease. See R. English et al.,
J. Am. Vet. Med. Assoc.
196:1116 (1990); N. Pedersen et al.,
Vet. Immunol. Immunopathol.
21:111 (1989); J. Yamamoto et al.,
J. Am. Vet. Med. Assoc.
194: 213 (1989). What is known to date of the pathogenesis of FIV infection suggests that it is a valuable animal model for other retroviral diseases, such as human immunodeficiency virus-1 (HIV-1) infection. HIV-1 and FIV belong to the lentivirus subfamily of retroviruses, have similar morphology, protein composition, and Mg
2+
-dependency of their reverse transcriptases (RT). See N. Pedersen et al.,
Science
235:790 (1987); N. Pedersen et al.,
Vet. Immunol. Immunopathol.
21:111 (1989). They both display tropism for T lymphocytes and monocytes and are capable of inducing these cells to form syncytia. See D. Brunner and N. Pedersen,
J. Virol.
63: 5483 (1989); M. Gardner and P. Luciw,
FASEB Journal
3: 2593 (1989). HIV-1 displays a particular tropism for CD4
+
lymphocytes, which leads to their gradual depletion and an inversion of the CD4
+
:CD8
+
ratio. See A. Dalgleish et al.,
Nature
312: 763 (1984). The pathogenesis of HIV-1 infection has been attributed to virus-induced reduction of CD4
+
lymphocyte numbers and functions, resulting in decreased immune responsiveness and subsequent severe secondary infections. See M. McChesney and M. Oldstone,
Ad. Immunol.
45: 335 (1989).
Yamamoto et al. studied the early events in the pathogenesis of FIV in kittens. See J. Yamamoto et al.,
Am. J. Vet. Res.
49: 1246 (1988). These kittens developed an acute infection syndrome similar to that seen in HIV-1, including low grade fever and transient generalized lymphadenopathy. More recent studies by Ackley et al.,
J. Virol.
64: 5652 (1990), utilized monoclonal antibodies directed against feline CD4
+
and CD8
+
homologues and Pan T cells to analyze lymphocyte profiles in SPF cats experimentally infected with FIV. These authors reported that a significant inversion of the CD4
+
:CD8
+
ratios occurred only in cats infected for 18 months or more. The inversion was associated with a decrease in absolute number of CD4
+
cells and an increase in CD8
+
cells.
A panel of monoclonal antibodies specific for feline T cell subsets (M. Tompkins et al.,
Vet. Immunol. Immunopathol.
26: 305 (1990)) has been used to analyze T cell numbers and profiles in cats naturally infected with FIV. See C. Novotney et al.,
AIDS
4: 1213 (1990). Similar to the observation of Ackley et al. supra, cats naturally infected with FIV have an inverted CD4
+
:CD8
+
ratio characterized by a selective reduction in CD4
+
cells.
SUMMARY OF THE INVENTION
A first aspect of the present invention is an isolated feline immunodeficiency virus (FIV) having all of the identifying characteristics of FIV clone JSY3.
A further aspect of the present invention is an isolated feline immunodeficiency virus (FIV) whose proviral DNA comprises a DNA sequence selected from SEQ ID NO:1 and sequences which vary from SEQ ID NO:1 due to the degeneracy of the genetic code.
A further aspect of the present invention is a biologically pure culture of host cells containing feline immunodeficiency virus as described above.
A further aspect of the present invention is isolated DNA comprising a DNA sequence selected from SEQ ID NO:1 and sequences which vary from SEQ ID NO:1 due to the degeneracy of the genetic code; vectors containing such DNA; and host cells containing and capable of expressing such vectors.
A further aspect of the present invention is isolated DNA comprising a DNA sequence selected from (a) SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, and (b) sequences which vary from those of (a) above due to the degeneracy of the genetic code; vectors containing such DNA; and host cells containing and capable of expressing such vectors.
A further aspect of the present invention is a polypeptide having a sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:15, SEQ ID NO:17, and SEQ ID NO:20.
A further aspect of the present invention is a specific pathogen free (SPF) cat infected with feline immunodeficiency virus clone JSY3.
REFERENCES:
patent: 5413927 (1995-05-01), Tompkins et al.
patent: 5736378 (1998-04-01), Elder et al.
Yamamoto, J.K., et al., 1995, Genbank Acc. Nos. L00608 and L00609.*
J. Yang et al.,Molecularly Cloned Feline Immunodeficiency Virus NCSU1JSY3 Induces Immunodeficiency in Specific-Pathogen-Free Cats,Jour. of Virology70(5):3011-3017 (1996).
J. Yang et al., Third Int'l Feline Retrovirus Research Symposium, Mar. 6-9, 1996 (Abstract).
Tompkins Mary
Tompkins Wayne
Yang Joo-Sung
Myers Bigel & Sibley & Sajovec
North Carolina State University
Parkin Jeffrey S.
Scheiner Laurie
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