4 Haematological disorders associated with feline retrovirus infections

Abstract

Feline oncornavirus and lentivirus infections have provided useful models to characterize the virus and host cell factors involved in a variety of marrow suppressive disorders and haematological malignancies. Exciting recent progress has been made in the characterization of the viral genotypic features involved in FeLV-associated diseases. Molecular studies have clearly defined the causal role of variant FeLV env gene determinants in two disorders: the T-lymphocyte cytopathicity and the clinical acute immunosuppression induced by the FeLV-FAIDS variant and the pure red cell aplasia induced by FeLV-C/Sarma. Variant or enFeLV env sequences also appear to play a role in FeLV-associated lymphomas. Additional studies are required to determine the host cell processes that are perturbed by these variant env gene products. In the case of the FeLV-FAIDS variant, the aberrant env gene products appear to impair superinfection interference, resulting in accumulation of unintegrated viral DNA and cell death. In other cases it is likely that the viral env proteins interact with host products that are important in cell viability and/or proliferation. Understanding of these mechanisms will therefore provide insights to factors involved in normal lymphohaematopoiesis. Similarly, studies of FeLV-induced haematological neoplasms should reveal recombination or rearrangement events involving as yet unidentified host gene sequences that encode products involved in normal cell growth regulation. These sequences may include novel protoncogenes or sequences homologous to genes implicated in human haematological malignancies. The haematological consequences of FIV are quite similar to those associated with HIV. As with HIV, FIV does not appear to directly infect myeloid or erythroid precursors, and the mechanisms of marrow suppression likely involve virus, viral antigen, and/or infected accessory cells in the marrow microenvironment. Studies using in vitro experimental models are required to define the effects of each of these microenvironmental elements on haematopoietic progenitors. As little is known about the molecular mechanisms of FIV pathogenesis, additional studies of disease-inducing FIV strains are needed to identify the genotypic features that correlate with virulent phenotypic features. Finally, experimental FIV infection in cats provides the opportunity to correlate in vivo virological and haematological changes with in vitro observations in a large animal model that closely mimics HIV infection in man.

Nonregenerative Anemia

“…41 In most anemic FeLV-infected cats, anemia is nonregenerative. 96 FeLV infects hematopoietic, lymphoid, and stromal cells in the marrow. 96 Of the 3 clinically important FeLV subgroups, FeLV-C has a unique erythrocytopathic effect.…”

“…96 FeLV infects hematopoietic, lymphoid, and stromal cells in the marrow. 96 Of the 3 clinically important FeLV subgroups, FeLV-C has a unique erythrocytopathic effect. While all FeLV subgroups have a similar hematopoietic cell tropism and may cause 1 or …”

“…Notably, FeLV infection is a risk factor for the development of myelodysplastic syndrome, lymphoma, and other hematologic malignancies. 78,96 Anemia is a less prominent feature of feline immunodeficiency virus (FIV) infection. Anemia (typically nonregenerative) has been reported in 31% of cats naturally infected with FIV and in 44% of cats with FIV and FeLV coinfection.…”

Inhibition of Xenotropic Murine Leukemia Virus-Related Virus by APOBEC3 Proteins and Antiviral Drugs

“…Gammaretroviruses infect a wide range of species and are associated with a variety of neurological and immunological disorders, as well as carcinomas and leukemias (9,11,21,30,58). In 2006, for the first time, a gammaretrovirus was isolated from human tissues and was named xenotropic murine leukemia virus-related virus (XMRV) (63).…”

“…In summary, the establishment of XMRV infection in patients may be dependent on infection of A3G/A3F-deficient cells, and cells expressing low levels of A3G/A3F, such as prostate cancer cells, may be ideal producers of infectious XMRV. Furthermore, the anti-HIV-1 drugs AZT, tenofovir, and raltegravir may be useful for treatment of XMRV infection.Gammaretroviruses infect a wide range of species and are associated with a variety of neurological and immunological disorders, as well as carcinomas and leukemias (9,11,21,30,58). In 2006, for the first time, a gammaretrovirus was isolated from human tissues and was named xenotropic murine leukemia virus-related virus (XMRV) (63).…”