Molecular and biological characterization of a neurovirulent molecular clone of simian immunodeficiency virus

Flaherty, M T; Hauer, Debra; Mankowski, Joseph L.; Zink, M. Christine; Clements, Janice E.

doi:10.1128/jvi.71.8.5790-5798.1997

Cited by 121 publications

(41 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study included 12 adult rhesus macaques (Macaca mulatta) negative for SIV, simian retrovirus (Type D), and simian T lymphotropic virus 1, 2 and 3. Eight adult rhesus macaques (M0798, M1998, M6598, M6798, M6998, M7098, M7198, and M7298) were inoculated with attenuated SIV mac 17E-Fred, a macrophage-tropic infectious molecular clone previously described [15] and characterized [28] in the rhesus macaque system. Between 14 and 18 months post-inoculation with SIV mac 17E-Fred, these eight animals were challenged twice with a pathogenic primary isolate, SIV/DeltaB670, once intrarectally and once intravenously.…”

Section: Immunization and Infection Of Animalsmentioning

confidence: 99%

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3⁺ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

Sarkar

Kalia

Murphey‐Corb

et al. 2003

J of Medical Primatology

View full text Add to dashboard Cite

Dysregulation of cytokines and chemokines during human immunodeficiency virus 1 (HIV-1) and simian immunodeficiency virus (SIV) infection is thought to be critical in the progression of acquired immunodeficiency syndrome (AIDS). To evaluate the potential role of Th1-agonist chemokines in disease progression during AIDS, we assessed CXCL9/MIG and CXCL10/IP-10 expression simultaneously in the periphery and lymphoid tissues of SIV-infected animals at a single-cell level by flow cytometry. We optimized intracellular staining and analysis of CXCL9/MIG and CXCL10/IP-10 production in human leukocyte antigen (HLA)-DR+ macaque cells by flow cytometry using cross-reactive antibodies against human chemokines. We observed an upregulation of CXCL9/MIG and CXCL10/IP-10 production in both the periphery and lymph nodes of infected animals compared with naïve controls. Animals with higher viral loads had higher levels of CXCL9/MIG and CXCL10/IP-10 producing cells compared with animals with low viral loads. Analysis of cells bearing the receptor (CXCR3) for CXCL9/MIG and CXCL10/IP-10 revealed increased number of CXCR3+ cells in the lymph nodes of infected animals. Importantly, an inverse correlation (P < 0.05) between CXCL9/MIG and CXCL10/IP-10 production, both in the periphery and lymph nodes, and peripheral CD4+ T-cell numbers was observed. These findings provide further evidence that dysregulation of Th1 agonist chemokines might contribute to the ultimate immunopathology during AIDS.

show abstract

Section: Immunization and Infection Of Animalsmentioning

confidence: 99%

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3⁺ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

Sarkar

Kalia

Murphey‐Corb

et al. 2003

J of Medical Primatology

View full text Add to dashboard Cite

show abstract

“…In fact, based on differences between EIAV UK and 19-2, confirmation of the result with viruses from EIAV PV101 would restrict these areas to two nucleotides in ORF S2 (at positions 4 and 19), potentially four nucleotides in ORF S3 (at positions 8, 14, 91, and 103), and two nucleotides in the TM glycoprotein (at positions 589 in the extracellular domain and 701 in the cytoplasmic domain). Interestingly, residues in TM in combination with SU sequences and an intact nef gene have recently been demonstrated to be essential for the optimal replication of SIV in brain cells derived from the micro-vessel endothelium and for SIV-mediated neurovirulence in macaques (16,37). Experiments are in progress to test the involvement of differences observed between EIAV UK and 19-2-6A in pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of an In Vivo Pathogenic Molecular Clone of Equine Infectious Anemia Virus

Cook

Leroux

Cook

et al. 1998

J Virol

View full text Add to dashboard Cite

An infectious nonpathogenic molecular clone (19-2-6A) of equine infectious anemia virus (EIAV) was modified by substitution of a 3.3-kbp fragment amplified by PCR techniques from a pathogenic variant (EIAVPV) of the cell culture-adapted strain of EIAV (EIAVPR). This substitution consisted of coding sequences for 77 amino acids at the carboxyl terminus of the integrase, the S1 (encoding the second exon of tat), S2, and S3 (encoding the second exon of rev) open reading frames, the complete env gene (including the first exon ofrev), and the 3′ long terminal repeat (LTR). Modified 19-2-6A molecular clones were designated EIAVPV3.3, and infection of a single pony (678) with viruses derived from a mixture of five of these molecular clones induced clinical signs of acute equine infectious anemia (EIA) at 23 days postinfection (dpi). As a consequence of this initial study, a single molecular clone, EIAVPV3.3#3 (redesignated EIAVUK), was selected for further study and inoculated into two ponies (613 and 614) and two horses (700 and 764). Pony 614 and the two horses developed febrile responses by 12 dpi, which was accompanied by a 48 to 64% reduction in platelet number, whereas pony 613 did not develop fever (40.6°C) until 76 dpi. EIAV could be isolated from the plasma of these animals by 5 to 7 dpi, and all became seropositive for antibodies to this virus by 21 dpi. Analysis of the complete nucleotide sequence demonstrated that the 3.3-kbp 3′ fragment of EIAVUKdiffered from the consensus sequence of EIAVPV by just a single amino acid residue in the second exon of the rev gene. Complete homology with the EIAVPV consensus sequence was observed in the hypervariable region of the LTR. However, EIAVUK was found to contain an unusual 68-bp nucleotide insertion/duplication in a normally conserved region of the LTR sequence. These results demonstrate that substitution of a 3.3-kbp fragment from the EIAVPV strain into the infectious nonpathogenic molecular clone 19-2-6A leads to the production of progeny virus particles with the ability to induce clinical signs of EIA. Therefore, EIAVUK, which is the first pathogenic, cell culture-adapted molecular clone of EIAV to be described, should be of value in identifying viral determinants of pathogenicity.

show abstract

“…Four juvenile pigtailed macaques ( Macaca nemestrina ) were inoculated intravenously with 10 4 tissue culture infectious doses (TCID 50 ) of SIV/17E‐Fr [10, 29]. SIV/17E‐Fr is a macrophage‐tropic, neurovirulent cloned recombinant virus derived from SIVmac239 by substituting the entire env and nef genes and the 3′ LTR with those of SIV/17E‐Br, a virus derived from SIVmac239 by serial passage in rhesus macaques, and isolated from the brain of a macaque with fulminant encephalitis [10, 29, 44].…”

Section: Methodsmentioning

confidence: 99%

SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy

Carruth

Zink

Tarwater³

et al. 2005

J of Medical Primatology

View full text Add to dashboard Cite

There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E-Fr and treated with combination antiretroviral therapy consisting of 9-R-(2-phosphonomethoxypropyl)adenine (PMPA) and beta-2',3'-dideoxy-3'-thia-5-fluorocytidine (FTC). The SIV-specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN-gamma Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV-specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus-specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus-specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.

show abstract

Molecular and biological characterization of a neurovirulent molecular clone of simian immunodeficiency virus

Cited by 121 publications

References 48 publications

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3⁺ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3⁺ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

Development and Characterization of an In Vivo Pathogenic Molecular Clone of Equine Infectious Anemia Virus

SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy

Contact Info

Product

Resources

About

Molecular and biological characterization of a neurovirulent molecular clone of simian immunodeficiency virus

Cited by 121 publications

References 48 publications

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3+ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3+ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

Development and Characterization of an In Vivo Pathogenic Molecular Clone of Equine Infectious Anemia Virus

SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy

Contact Info

Product

Resources

About

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3⁺ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

Expression of IFN‐γ induced CXCR3 agonist chemokines and compartmentalization of CXCR3⁺ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome