scholarly journals Experimental transmission and pathogenesis of immunodeficiency syndrome in cats

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1880-1892 ◽  
Author(s):  
EA Hoover ◽  
JI Mullins ◽  
SL Quackenbush ◽  
PW Gasper
Keyword(s):  
Viral Replication ◽  
Opportunistic Infections ◽  
Feline Leukemia Virus ◽  
In Vivo Model ◽  
Lymphoid Tissues ◽  
Experimental Transmission ◽  
Lymphoid Follicles ◽  
Immunodeficiency Disease ◽  
Immunodeficiency Syndrome

Abstract We describe the identification, experimental transmission, and pathogenesis of a naturally occurring powerfully immunosuppressive isolate of feline leukemia virus (designated here as FeLV-FAIDS) which induces fatal acquired immunodeficiency syndrome (AIDS) in 100% (25 of 25) of persistently viremic experimentally infected specific pathogen- free (SPF) cats after predictable survival periods ranging from less than 3 months (acute immunodeficiency syndrome) to greater than one year (chronic immunodeficiency syndrome), depending on the age of the cat at time of virus exposure. The pathogenesis of FeLV-FAIDS-induced feline immunodeficiency disease is characterized by: a prodromal period of largely asymptomatic viremia; progressive weight loss, lymphoid hyperplasia associated with viral replication in lymphoid follicles, lymphoid depletion associated with extinction of viral replication in lymphoid follicles, intractable diarrhea associated with necrosis of intestinal crypt epithelium, lymphopenia, suppressed lymphocyte blastogenesis, impaired cutaneous allograft rejection, hypogammaglobulinemia, and opportunistic infections such as bacterial respiratory disease and necrotizing stomatitis. The clinical onset of immunodeficiency syndrome correlates with the replication of a specific FeLV-FAIDS viral variant, detected principally as unintegrated viral DNA, in bone marrow, lymphoid tissues, and intestine. Two of seven cats with chronic immunodeficiency disease that survived greater than 1 year after inoculation developed lymphoma affecting the marrow, intestine, spleen, and mesenteric nodes. Experimentally induced feline immunodeficiency syndrome, therefore, is a rapid and consistent in vivo model for prospective studies of the viral genetic determinants, pathogenesis, prevention, and therapy of retrovirus-induced immunodeficiency disease.

scholarly journals Experimental transmission and pathogenesis of immunodeficiency syndrome in cats

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1880-1892
Author(s):  
EA Hoover ◽  
JI Mullins ◽  
SL Quackenbush ◽  
PW Gasper
Keyword(s):  
Viral Replication ◽  
Opportunistic Infections ◽  
Feline Leukemia Virus ◽  
In Vivo Model ◽  
Lymphoid Tissues ◽  
Experimental Transmission ◽  
Lymphoid Follicles ◽  
Immunodeficiency Disease ◽  
Immunodeficiency Syndrome

We describe the identification, experimental transmission, and pathogenesis of a naturally occurring powerfully immunosuppressive isolate of feline leukemia virus (designated here as FeLV-FAIDS) which induces fatal acquired immunodeficiency syndrome (AIDS) in 100% (25 of 25) of persistently viremic experimentally infected specific pathogen- free (SPF) cats after predictable survival periods ranging from less than 3 months (acute immunodeficiency syndrome) to greater than one year (chronic immunodeficiency syndrome), depending on the age of the cat at time of virus exposure. The pathogenesis of FeLV-FAIDS-induced feline immunodeficiency disease is characterized by: a prodromal period of largely asymptomatic viremia; progressive weight loss, lymphoid hyperplasia associated with viral replication in lymphoid follicles, lymphoid depletion associated with extinction of viral replication in lymphoid follicles, intractable diarrhea associated with necrosis of intestinal crypt epithelium, lymphopenia, suppressed lymphocyte blastogenesis, impaired cutaneous allograft rejection, hypogammaglobulinemia, and opportunistic infections such as bacterial respiratory disease and necrotizing stomatitis. The clinical onset of immunodeficiency syndrome correlates with the replication of a specific FeLV-FAIDS viral variant, detected principally as unintegrated viral DNA, in bone marrow, lymphoid tissues, and intestine. Two of seven cats with chronic immunodeficiency disease that survived greater than 1 year after inoculation developed lymphoma affecting the marrow, intestine, spleen, and mesenteric nodes. Experimentally induced feline immunodeficiency syndrome, therefore, is a rapid and consistent in vivo model for prospective studies of the viral genetic determinants, pathogenesis, prevention, and therapy of retrovirus-induced immunodeficiency disease.

scholarly journals Colony forming T lymphocyte deficit in the development of feline retrovirus induced immunodeficiency syndrome

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 509-516 ◽  
Author(s):  
SL Quackenbush ◽  
JI Mullins ◽  
EA Hoover
Keyword(s):  
T Lymphocyte ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Lymphoid Tissues ◽  
Prodromal Phase ◽  
Time Period ◽  
Immunodeficiency Disease ◽  
Immunodeficiency Syndrome ◽  
Colony Forming Assay ◽  
Prospective Investigation

Abstract The identification and molecular cloning of a feline leukemia virus (FeLV) isolate (FeLV-FAIDS) that consistently produces immunodeficiency syndrome has allowed prospective investigation of events that occur in the prodromal phase of disease. Using a T-lymphocyte colony forming assay (T-CFU-Ic) we have demonstrated that a drastic depletion of circulating T-CFU-Ic prefigures the development of clinical immunodeficiency disease in inoculated cats and correlates with the appearance and replication of the FeLV-FAIDS variant genome in serially collected bone marrow samples. During the same presymptomatic time period, no significant alterations in conventional mitogen-induced lymphocyte blastogenic responses or in circulating lymphocyte numbers were evident. Thus T-CFU-Ic assay but not conventional mitogen-driven blastogenesis identified animals destined to develop immunodeficiency syndrome. The correlation among T-CFU-Ic depletion, the replication of the lymphocytopathic FeLV-FAIDS variant genome in hematopoietic and lymphoid tissues, and the onset of clinical disease, infers that ablation of a colony-forming T lymphocyte progenitor subset is important in the early pathogenesis of feline retrovirus-induced immunodeficiency syndrome.

scholarly journals Colony forming T lymphocyte deficit in the development of feline retrovirus induced immunodeficiency syndrome

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 509-516
Author(s):  
SL Quackenbush ◽  
JI Mullins ◽  
EA Hoover
Keyword(s):  
T Lymphocyte ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Lymphoid Tissues ◽  
Prodromal Phase ◽  
Time Period ◽  
Immunodeficiency Disease ◽  
Immunodeficiency Syndrome ◽  
Colony Forming Assay ◽  
Prospective Investigation

The identification and molecular cloning of a feline leukemia virus (FeLV) isolate (FeLV-FAIDS) that consistently produces immunodeficiency syndrome has allowed prospective investigation of events that occur in the prodromal phase of disease. Using a T-lymphocyte colony forming assay (T-CFU-Ic) we have demonstrated that a drastic depletion of circulating T-CFU-Ic prefigures the development of clinical immunodeficiency disease in inoculated cats and correlates with the appearance and replication of the FeLV-FAIDS variant genome in serially collected bone marrow samples. During the same presymptomatic time period, no significant alterations in conventional mitogen-induced lymphocyte blastogenic responses or in circulating lymphocyte numbers were evident. Thus T-CFU-Ic assay but not conventional mitogen-driven blastogenesis identified animals destined to develop immunodeficiency syndrome. The correlation among T-CFU-Ic depletion, the replication of the lymphocytopathic FeLV-FAIDS variant genome in hematopoietic and lymphoid tissues, and the onset of clinical disease, infers that ablation of a colony-forming T lymphocyte progenitor subset is important in the early pathogenesis of feline retrovirus-induced immunodeficiency syndrome.

scholarly journals CD4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS).

1988 ◽  
Vol 168 (2) ◽  
pp. 623-635 ◽  
Author(s):  
R A Yetter ◽  
R M Buller ◽  
J S Lee ◽  
K L Elkins ◽  
D E Mosier ◽  
...  
Keyword(s):  
T Cells ◽  
Normal Serum ◽  
Spleen Cells ◽  
Th Cells ◽  
Immunodeficiency Disease ◽  
Immunodeficiency Syndrome ◽  
Leukemia Viruses ◽  
Murine Leukemia ◽  
Ctl Responses

Mice depleted in vivo of CD4+ Th cells by treatment with mAb GK1.5 were found to be resistant to the lymphoproliferative/immunodeficiency disease (MAIDS) induced in intact mice by infection with the mixture of LP-BM5 murine leukemia viruses. Depleted mice did not develop lymphadenopathy or splenomegaly, had normal serum IgM levels, normal CTL responses to alloantigens, and were able to generate PFC responses to Th-independent antigens even though frequencies of virus-producing spleen cells were comparable in depleted and intact mice. Depletion of CD4+ Th cells after infection resulted in a reversal of many abnormalities exhibited by infected controls; spleen weights, serum IgM levels, and allogeneic CTL responses of treated mice were comparable to those of uninfected controls. These results demonstrate that dysfunction of CD4+ Th cells is central to the induction and progression of both T and B cell abnormalities in MAIDS.

scholarly journals Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1393-1398 ◽  
Author(s):  
RK Akkina ◽  
JD Rosenblatt ◽  
AG Campbell ◽  
IS Chen ◽  
JA Zack
Keyword(s):  
Gene Therapy ◽  
In Vivo Model ◽  
Hematopoietic Stem ◽  
Gene Therapies ◽  
Human Cd34 ◽  
Human T Lymphocyte ◽  
Thymocyte Differentiation ◽  
Immunodeficiency Syndrome

Abstract Gene therapy of human T-lymphocyte disorders, including acquired immunodeficiency syndrome (AIDS), would be greatly facilitated by the development of an in vivo system in which transduced human hematopoietic stem cells can be used to reconstitute the T-lymphoid compartment. Here we use the SCID-hu mouse as a recipient for human CD34+ hematopoietic progenitor cells transduced in vitro with a retroviral vector carrying the neomycin resistance gene (neoR). The transduced cells engraft and reconstitute the lymphoid compartments of the human thymus implant with as few as 5 x 10(4) CD34+ cells. The neoR gene was expressed at low levels in human thymocytes and there was no apparent effect on thymocyte differentiation as a result of vector transduction. Thus, this SCID-hu mouse system is the first in vivo model showing human thymopoiesis after transduction of exogenous vectors, and should allow preclinical testing of gene therapeutic reagents designed to function in human cells of the T-lymphoid lineage. Because human immunodeficiency virus type 1 infection induces depletion of human thymocytes in SCID-hu mice, this system may be particularly valuable in evaluating efficacy of gene therapies to combat AIDS.

scholarly journals Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development of Kaposi's sarcoma-like lesions in BALB/c nu/nu mice.

1994 ◽  
Vol 180 (5) ◽  
pp. 1949-1954 ◽  
Author(s):  
P J Browning ◽  
D D Roberts ◽  
V Zabrenetzky ◽  
J Bryant ◽  
M Kaplan ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Oncostatin M ◽  
In Vivo Model ◽  
Heparin Binding ◽  
Heparin Binding Protein ◽  
Immunodeficiency Syndrome

Recombinant apolipoprotein E-3 (ApoE-3), expressed in Escherichia coli, was purified and used in an in vitro and an in vivo model system for acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). This protein blocked cell proliferation and chemotaxis of AIDS-KS cells in response to activated lymphocyte conditioned medium (AL-CM) and oncostatin M (OSM). ApoE-3 also inhibited the formation of neoangiogenic lesions induced in BALB/c nu/nu mice by AIDS-KS cells. These findings represent a novel and potentially less toxic therapeutic approach for the treatment of AIDS-KS.

scholarly journals Saquinavir-mediated inhibition of human immunodeficiency virus (HIV) infection in SCID mice implanted with human fetal thymus and liver tissue: an in vivo model for evaluating the effect of drug therapy on HIV infection in lymphoid tissues.

1997 ◽  
Vol 41 (9) ◽  
pp. 1880-1887 ◽  
Author(s):  
M Pettoello-Mantovani ◽  
T R Kollmann ◽  
C Raker ◽  
A Kim ◽  
S Yurasov ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Scid Mice ◽  
Therapeutic Interventions ◽  
In Vivo Model ◽  
Lymphoid Tissues ◽  
Hiv Replication ◽  
Viral Loads ◽  
Immunodeficiency Virus

Treatment with protease inhibitors alone or in combination with inhibitors of reverse transcriptase potently suppresses levels of human immunodeficiency virus (HIV) RNA in plasma and thereby may significantly delay the progression of HIV-mediated disease. To investigate the effect of treatment with the protease inhibitor saquinavir on HIV replication in the lymphoid tissues, we used a SCID-hu mouse model that we developed, in which human thymic and liver tissues (hu-thy/liv) were implanted under both kidney capsules in SCID mice (thy/liv-SCID-hu mice). These mice are populated in the periphery with large numbers of human T cells and develop disseminated HIV infection after intraimplant injection. thy/liv-SCID-hu mice with established HIV infection that were treated for 1 month with saquinavir had a significantly lower viral load present in the implanted hu-thy/liv and mouse spleen than did the untreated HIV-infected thy/liv-SCID-hu mice. To examine the capacity of acute treatment with saquinavir to prevent HIV infection, some thy/liv-SCID-hu mice were inoculated with HIV and then immediately started on saquinavir. Although treated mice had markedly lower viral loads in the thy/liv implants and spleens, HIV infection was not completely prevented. Thus, the effect of antiviral therapy on HIV infection in the major site of HIV replication, the lymphoid tissues, can be readily evaluated in our thy/liv-SCID-hu mice. These mice should prove to be a useful model for determining the in vivo effectiveness of different therapeutic interventions on acute and chronic HIV infection.

scholarly journals Cellular HIV Reservoirs and Viral Rebound from the Lymphoid Compartments of 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine (EFdA)-Suppressed Humanized Mice

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 256 ◽  
Author(s):  
Ekaterina Maidji ◽  
Mary Moreno ◽  
Jose Rivera ◽  
Pheroze Joshi ◽  
Sofiya Galkina ◽  
...  
Keyword(s):  
Transcriptase Inhibitor ◽  
Humanized Mice ◽  
In Vivo Model ◽  
Lymphoid Tissues ◽  
Viral Rebound ◽  
Hiv Reverse Transcriptase ◽  
Hiv Reservoirs ◽  
Hiv Reservoir ◽  
Drug Cessation

Although antiretroviral therapy (ART) greatly suppresses HIV replication, lymphoid tissues remain a sanctuary site where the virus may replicate. Tracking the earliest steps of HIV spread from these cellular reservoirs after drug cessation is pivotal for elucidating how infection can be prevented. In this study, we developed an in vivo model of HIV persistence in which viral replication in the lymphoid compartments of humanized mice was inhibited by the HIV reverse transcriptase inhibitor 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) to very low levels, which recapitulated ART-suppression in HIV-infected individuals. Using a combination of RNAscope in situ hybridization (ISH) and immunohistochemistry (IHC), we quantitatively investigated the distribution of HIV in the lymphoid tissues of humanized mice during active infection, EFdA suppression, and after drug cessation. The lymphoid compartments of EFdA-suppressed humanized mice harbored very rare transcription/translation-competent HIV reservoirs that enable viral rebound. Our data provided the visualization and direct measurement of the early steps of HIV reservoir expansion within anatomically intact lymphoid tissues soon after EFdA cessation and suggest a strategy to enhance therapeutic approaches aimed at eliminating the HIV reservoir.

scholarly journals Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1393-1398 ◽  
Author(s):  
RK Akkina ◽  
JD Rosenblatt ◽  
AG Campbell ◽  
IS Chen ◽  
JA Zack
Keyword(s):  
Gene Therapy ◽  
In Vivo Model ◽  
Hematopoietic Stem ◽  
Gene Therapies ◽  
Human Cd34 ◽  
Human T Lymphocyte ◽  
Thymocyte Differentiation ◽  
Immunodeficiency Syndrome

Gene therapy of human T-lymphocyte disorders, including acquired immunodeficiency syndrome (AIDS), would be greatly facilitated by the development of an in vivo system in which transduced human hematopoietic stem cells can be used to reconstitute the T-lymphoid compartment. Here we use the SCID-hu mouse as a recipient for human CD34+ hematopoietic progenitor cells transduced in vitro with a retroviral vector carrying the neomycin resistance gene (neoR). The transduced cells engraft and reconstitute the lymphoid compartments of the human thymus implant with as few as 5 x 10(4) CD34+ cells. The neoR gene was expressed at low levels in human thymocytes and there was no apparent effect on thymocyte differentiation as a result of vector transduction. Thus, this SCID-hu mouse system is the first in vivo model showing human thymopoiesis after transduction of exogenous vectors, and should allow preclinical testing of gene therapeutic reagents designed to function in human cells of the T-lymphoid lineage. Because human immunodeficiency virus type 1 infection induces depletion of human thymocytes in SCID-hu mice, this system may be particularly valuable in evaluating efficacy of gene therapies to combat AIDS.

scholarly journals Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever

2019 ◽  
Vol 4 (2) ◽  
pp. 63 ◽  
Author(s):  
Min Min Win ◽  
Komgrid Charngkaew ◽  
Nuntaya Punyadee ◽  
Khin Saw Aye ◽  
Ne Win ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Viral Replication ◽  
Virus Replication ◽  
Dengue Hemorrhagic Fever ◽  
Structural Changes ◽  
Cell Model ◽  
Hemorrhagic Fever ◽  
In Vivo Model ◽  
Suckling Mouse

Recent advances in electron microscopy and tomography have revealed distinct virus-induced endoplasmic reticulum (ER) structures unique for dengue virus (DV) and other flaviviruses in cell culture models, including hepatocytes. These altered ultrastructures serve as sites for viral replication. In this study, we used transmission electron microscopy to investigate whether such structures were present in the liver of fatal dengue hemorrhagic fever (DHF) autopsy cases. In parallel, electron microscopic examination of suckling mouse brains experimentally infected with DV was performed as an in vivo model of acute DV infection. Typical features of ER changes containing abundance of replicative virions were observed in neurons and microglia of DV-infected suckling mouse brains (SMB). This indicated that the in vivo DV infection could induce similar viral replication structures as previously described in the in vitro DV-infected cell model. Nevertheless, liver tissues from autopsy of patients who died of DHF showed scant changes of ER membrane structures and rare particles of virions in hepatocytes, despite overwhelming evidence for the presence of viral antigens and RNA–indicating active virus replication. Instead hepatocytes contained an abundance of steatotic vesicles and structural damages. This lack of structural changes indicative of virus replication in human hepatocytes is discussed.

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