Replication and Pathogenesis of the Human T-Cell Leukemia/Lymphotropic Retroviruses (original) (raw)
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Tumorigenesis related to retroviral infections
The Journal of Infection in Developing Countries, 2011
Retroviral infections are considered important risk factors for cancer development in humans since approximately 15-20% of cancer worldwide is caused by an infectious agent. This report discusses the most established oncogenic retroviruses, including human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1 and -2), Rous sarcoma virus (RSV), Abelson murine leukemia virus (A-MuLV), Moloney murine leukemia virus (M-MuLV), murine mammary tumor virus (MMTV), bovine leukemia virus, (BLV), Jaagsiekte sheep retrovirus (JSRV), and Friend spleen focus-forming virus (SFFV). The role of retroviruses as inducers of carcinogenesis, the mechanisms underlying oncogenic transformation, and the routes of transmission of several cancer-related retroviral infections are also described. Finally, the impact of cancer-related retroviral infections in the developing world is addressed. This review is an update of carcinogenesis caused by retroviral infections.
Leukemia and Retroviral Disease
Leukemias - Updates and New Insights, 2015
Two human retroviruses, identified as the human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1), have been shown to affect millions of people worldwide. In the context of coinfection, the impact of their interactions with respect to HTLV-1-induced adult T-cell leukemia and neurologic disease as well as HIV-1 disease progression has been an understudied area of investigation. HTLV-1/HIV-1 coinfections occur frequently, particularly in large metropolitan areas of the Americas, Africa, Europe, and Japan. The retroviruses HTLV-1 and HIV-1 share some similarities with regard to their genetic structure, general mechanisms of replication, modes of transmission, and cellular tropism; however, there are also significant differences in the details of these properties as well, and they also differ significantly with respect to the etiology of their pathogenic and disease outcomes. Both viruses impair the host immune system with HIV-1 demonstrated to cause the hallmark lethal disease known as the acquired immune deficiency syndrome (AIDS), while HTLV-1 infection has been shown to cause several different forms of T-cell leukemia. In addition, both viruses have also been shown to cause a spectrum of neurologic disorders with HIV-1 shown to cause an array of neurologic syndromes referred to as HIV-1-associated neurologic disorders or HAND, while HTLV-1 has been shown to be the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis or HAM/TSP. The natural history of the coinfection, however, is different from that observed in monoinfections. Several studies have demonstrated utilizing a number of in vitro models of HTLV-1/HIV-1 coinfection that the two viruses interact in a manner that results in enhanced expression of both viral genomes. Nevertheless, there remains unresolved controversy regarding the overall impact of each virus on progression of disease caused by both viruses during the course of coinfection. Although combination antiretroviral therapy has been shown to work very effectively with respect to maintaining HIV-1 viral loads in the undetectable range, these therapeutic strategies exhibit no benefit for HTLV-1-infected individuals, unless administered immediately after exposure. Furthermore, the treatment options for HTLV-1/HIV-1-coinfected patients are very limited. In recent years, allogeneic stem cell transplantation (alloSCT) has been used for
Cancer, 1985
The human T-cell leukemia virus type-] (HTLV-I) is a unique, exogenous, horizontally transmitted retrovirus which is T-cell tropic, and has been associated with a specific type of aggressive leukemia/ lymphoma of mature T-cell origin. In a Survey of lymphoid malignancies in Jamaia, antimies to HTLV-I were also found in 6 of 17 patients with chronic. lyrnphocytic leukemia (CLL), raising the possibiiity of an etiologic relatianship. Further studies were undertaken on one of these padents to clarify the nature of the disease and possible virus relationship. CeH surface marker analysis of her peripheral b l w d cells documented that the majority of circulating lymphocytes were B-cells. DNAcloned probe analysis with a complete HTLV-I proviral genome of these peripheral malignant B-cells, was negative for intwated virus. A Txell line was established in culture from her peripheral blood. The presence of HTLV-I in the cultured T-cell line was established by the detection of expressed viral specific gag protein p-19 and proviral DNA. Thus, a B-cell lymphoid malignancy can occur in the presence of HTLV-I infected T-cells, suggesting the possibility of an indirect leukemogenic mechanism. Cmcer 56:495-499, 1985. T wo DIsTrNCr but distantly related type-C retroviruses, HTLV-I and HTLV-11, have been isolated and characterized from humans with T-cell malignanciw.Ib2 Both HTLV-I and HTLV-I1 infect and transform T-~ells.~+' HTLV-I infection has been previously linked with a specific type of human adult T-cell leukemia/ lymphoma (ATL) which is found primarily in areas where HTLV-I infection is endemic in the general ~p~l a t i o n .~,~ Taken together, these data clearly link HTLV-1 to the cause of some human T-cell malignancies. Funk t: :nore, surprisingly, antibodies t o the virus have k e n detected in certain other types of leukemias from -' Environmental Epidemiolw Branch,
Journal of …, 1996
and HTLV-1-associated myelopathy-tropical spastic paraparesis. We examined whether HTLV could productively infect human hematopoietic progenitor cells. CD34 ؉ cells were enriched from human fetal liver cells and cocultivated with cell lines transformed with HTLV-1 and -2. HTLV-1 infection was established in between 10 and >95% of the enriched CD34 ؉ cell population, as demonstrated by quantitative PCR analysis. HTLV-1 p19 Gag expression was also detected in infected hematopoietic progenitor cells. HTLV-1-infected hematopoietic progenitor cells were cultured in semisolid medium permissive for the development of erythroid (BFU-E), myeloid (CFU-GM), and primitive progenitor (CFU-GEMM, HPP-CFC, or CFU-A) colonies. HTLV-1 sequences were detected in colonies of all hematopoietic lineages; furthermore, the ratio of HTLV genomes to the number of human cells in each infected colony was 1:1, consistent with each colony arising from a single infected hematopoietic progenitor cell. Severe combined immunodeficient mice engrafted with human fetal thymus and liver tissues (SCID-hu) develop a conjoint organ which supports human thymocyte differentiation and maturation.