Equine infectious anemia virus (EIAV) is an equine lentivirus responsible for a persistent infection manifested by recurring episodes of fever, anemia and edema. Each episode of clinical disease is associated with the emergence of a unique antigenic variant of EIAV. During phase I, this project will attempt to develop an infectious molecular clone of EIAV from genomic RNA extracted from the plasma of a pony acutely infected with the wild-type Wyoming strain of EIAV. We will determine the entire nucleotide sequence of this infectious clone using the dideoxy, chain terminating method of sequencing. Comparison of the nucleotide sequence of this infectious, virulent clone with previously developed avirulent, noninfectious clones will help define some molecular determinants of infectivity. In addition, combined in situ hybridization and immunocytochemical studies using monoclonal antibodies to equine monocytes/macrophages and EIAV will be performed. This will allow identification of cellular sites of viral replication and persistence during acute disease and during the chronic, asymptomatic stage of infection. During Phase II, ponies will be infected with the infectious, virulent clone of wild-type Wyoming strain of EIAV. Virus isolates from sequential febrile episodes will be analyzed by oligonucleotide mapping to determine sites and types of nucleotide mutations occurring in vivo. Molecular determinants of infectivity and virulence will be further investigated using serial allelic replacements of nucleotide segments of noninfectious avirulent clones with comparable segments from our infectious clones. Taken together, the proposed experiments should provide much-needed information on mechanisms of lentivirus persistence and in vivo antigenic variation following an initial homogeneous infection. These same mechanisms may be integral in the pathogenesis of human lentivirus infections, including the acquired immune deficiency syndrome (AIDS) associated with human immunodeficiency virus 1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Physician Scientist Award (K11)
Project #
1K11AI000963-01
Application #
3085339
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Project Start
1990-09-30
Project End
1995-08-31
Budget Start
1990-09-30
Budget End
1991-08-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
North Carolina State University Raleigh
Department
Type
Schools of Veterinary Medicine
DUNS #
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Sellon, D C; Russell, K E; Monroe, V L et al. (1999) Increased interleukin-6 activity in the serum of ponies acutely infected with equine infectious anaemia virus. Res Vet Sci 66:77-80
Russell, K E; Perkins, P C; Hoffman, M R et al. (1999) Platelets from thrombocytopenic ponies acutely infected with equine infectious anemia virus are activated in vivo and hypofunctional. Virology 259:7-19
Sellon, D C; Walker, K M; Russell, K E et al. (1996) Equine infectious anemia virus replication is upregulated during differentiation of blood monocytes from acutely infected horses. J Virol 70:590-4
Sellon, D C; Walker, K M; Russell, K E et al. (1996) Phorbol ester stimulation of equine macrophage cultures alters expression of equine infectious anemia virus. Vet Microbiol 52:209-21
Sellon, D C (1993) Equine infectious anemia. Vet Clin North Am Equine Pract 9:321-36
Sellon, D C; Cullen, J M; Whetter, L E et al. (1993) Production and characterization of a monoclonal antibody recognizing a cytoplasmic antigen of equine mononuclear phagocytes. Vet Immunol Immunopathol 36:303-18
Perry, S T; Flaherty, M T; Kelley, M J et al. (1992) The surface envelope protein gene region of equine infectious anemia virus is not an important determinant of tropism in vitro. J Virol 66:4085-97
Sellon, D C; Perry, S T; Coggins, L et al. (1992) Wild-type equine infectious anemia virus replicates in vivo predominantly in tissue macrophages, not in peripheral blood monocytes. J Virol 66:5906-13
Clabough, D L; Gebhard, D; Flaherty, M T et al. (1991) Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus. J Virol 65:6242-51