The present invention relates to a novel retrovirus, a spumavirus, that has been isolated from a human. More particularly, the novel spumavirus may be used as a vector for gene therapy or as a recombinant virus vaccine. The invention can also serve as a reagent in pathogenicity studies of related viruses and be used to screen for spumavirus infection in humans.
Spumavirus, also known as foamy virus for the characteristics of vacuolization the virus induces in cell culture, belongs to a distinct group of retroviruses. The simian foamy viruses (SFVs) include isolates from Old World and New World monkeys and are classified into 10 different serotypes based on serological cross-reactivities. Virus appears to persist in the host for a long period of time in a latent form and can exist in the presence of neutralizing antibody.
Currently the most studied retrovirus, human immunodeficiency virus (HIV), is believed to be derived from non-human primate transmission into humans at some past time. Concerns about the risk of transmission of retroviruses from non-human primates (NHP) to humans working in research laboratories were heightened in the early 1990""s when two persons developed antibodies to SIV (simian immunodeficiency virus) following work-related exposures, one of whom had clear evidence of persistent viral infection. (See CDC Anonymous survey for simian immunodeficiency virus (SIV) seropositivity in SIV laboratory researchersxe2x80x94United States, 1992. MMWR Morb. Mort. Wkly. Rep. 1992; 41: 814-5; Khabbaz R. F., et al. Brief report: infection of a laboratory worker with simian immunodeficiency virus. New Eng. J. Med. 1994; 330: 172-7; Khabbaz R. F., et al. Simian immunodeficiency virus needlestick accident in a laboratory worker. Lancet 1992; 340: 271-3; and CDC. Guideline to prevent simian immunodeficiency virus infection in laboratory workers and animal handlers. MMWR 1988; 37:693-704.) In addition to SIV, non-human primate species used in biomedical research are commonly infected with SFV (simian foamy virus), STLV (simian t-cell lymphotrophic virus), and/or type D retroviruses. All of these retroviruses cause lifelong infections in NHP, and some are known to be transmissible through sexual contact, blood, or breast feeding. Natural SFV infections in non-human primates have not been definitively associated with disease. In NHP, infection with the other retroviruses may result in a clinical spectrum ranging from asymptomatic infection to life threatening immunodeficiency syndromes or lymphoproliferative disorders. The transmission routes of SFVs among non-human primates remain undefined, but the prevalence of seroreactivity is high among captive adult non-human primates.
Studies of the prevalence of spumavirus infection of humans are limited and the findings are not definitive. Though there is some evidence of human infection with SFV (antibodies and positive PCR results), such occurrence has been reported in only two persons, both of whom had occupational risks for infection. Associated disease was not reported in either. (See Schweizer M., et al. Absence of foamy virus DNA in Graves"" disease. AIDS Res. and Human Retrov. 1994; 10: 601-5; Neumann-Haefelin D., et al., Foamy viruses. Intervirology 1993; 35: 196-207; and Schweizer M., et al., Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans. AIDS Res. and Human Retrov. 1995; 11: 161-70).
Other inconclusive evidence was seen in early studies which described a relatively high rate of seroreactivity to antibodies to spumaviruses among human populations not known to be exposed to non-human primates. In some instances seroreactivity was suggestively linked to human disease, including disorders of the central nervous system, thyroid disease, and Chronic Fatigue Syndrome. In most instances these studies lacked definitive evidence of human infection and were not subsequently confirmed (See Heneine, W., et al., Absence of evidence for human spumaretrovirus sequences in patients with Graves"" disease [letter]. J. Acq. Immune Defic. Synd. and Human Retrov. 1995; 9: 99-101; Simonsen, L., et al.,. Absence of evidence for infection with the human spumaretrovirus in an outbreak of Meniere-like vertiginous illness in Wyoming, USA [letter]. Acta Oto-Laryngologica 1994; 114: 223-4; and Heneine, W., et al., Lack of evidence for infection with known human and animal retroviruses in patients with chronic fatigue syndrome. Clin. Infect. Dis. 1994; 18: S121-5).
Recent publications indicate that earlier serological tests showing human spumavirus antibodies in the human population were incorrect. Immunological investigation of a previously reported human spumavirus revealed that it shared common antigens in complement fixation, immunofluorescence and neutralization assays with the chimpanzee foamy virus, SFV-6. The virus known as HFV, Human Foamy Virus was derived from a nasocarcinoma and is now believed not to be a human foamy virus, but a chimpanzee virus. Failure to detect serological evidence of HFV infection in people from a wide geographical area suggested that this virus isolate was a variant of SFV-6, particularly since sera from chimpanzees naturally infected with SFV-6 neutralized both viruses. In a survey for prevalence of HFV in more than 5000 human sera, collected from geographically diverse populations, none of the serum samples were confirmed as positive. Taken together with sequence analysis endorsing the phylogenetic closeness of the purported human spumavirus to SFV-6, these data strongly suggest that HIV is not naturally found in the human population. (See AH, M. et al., xe2x80x9cNo evidence of antibody to Human Foamy Virus in widespread human populations,xe2x80x9d AIDS Research and Human Retroviruses, Vol. 12, No. 15, 1996).
Novel human spumaviruses have been found in humans who were exposed to nonhuman primates. These novel viruses are unique viruses that reproduce in humans and yet cause no disease. These viruses are disclosed in U.S. Pat. No. 5,882,912 and U.S. patent application Ser. No. 60/105,811, incorporated in their entirety herein. The existence of new human retroviruses in humans that were derived originally from simian sources indicates a need for compositions and methods for the immunological screening of the human population for the prevalence of spumavirus infection as web as for the screening of the human blood supply.
Recent concern that xenotransplantation, the use of living tissues from nonhuman species in humans for medical purposes, may introduce new infections into the human community has increased the importance of defining the ability of simian retroviruses to infect and/or cause disease in humans (See Chapman, L. E., et al. Xenotransplantation and xenogeneic infections. New Engl. J. Med. 1995; 333: 1498-1501; DHHS. Docket No. 96M0311. Draft Public Health Service (PHS) Guideline on Infectious