SIV adaptation to human cells.
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Amino Acid Sequence↗
Biomedical subjects
V M Hirsch
Publications and source records attributed to V M Hirsch.
An African primate lentivirus (SIVsm) closely related to HIV-2.
The ancestors of the human immunodeficiency viruses (HIV-1 and HIV-2) may have evolved from a reservoir of African nonhuman primate lentiviruses, termed simian immunodeficiency viruses (SIV). None of the SIV strains characterized so far are closely related to HIV-1. HIV-2, however, is closely related to SIV (SIVmac) isolated from captive rhesus macaques (Macaca mulatta). SIV infection of feral Asian macaques has not been demonstrated by serological surveys. Thus, macaques may have acquired SIV in captivity by cross-species transmission from an SIV-infected African primate. Sooty mangabeys (Cercocebus atys), an African primate species indigenous to West Africa, however, are infected with SIV (SIVsm) both in captivity and in the wild (P. Fultz, personal communication). We have molecularly cloned and sequenced SIVsm and report here that it is closely related to SIVmac and HIV-2. These results suggest that SIVsm has infected macaques in captivity and humans in West Africa and evolved as SIVmac and HIV-2, respectively.
Africa↗
Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses.
We determined the complete nucleotide sequence of an infectious proviral molecular clone (FIV-14) of the feline immunodeficiency virus (FIV). FIV-14 has a genome organization similar in complexity to other lentiviruses. In addition to three large open reading frames representing the gag, pol, and env genes, at least four small open reading frames are present in the pol-env intergenic, env, and env-3' long terminal repeat regions. Nucleotide and deduced amino acid sequence alignments of the FIV coding sequences with analogous sequences of other lentiviruses revealed significant identities only in the gag and pol genes. Phylogenetic tree analyses of gag and pol gene-encoded protein sequences demonstrate that FIV is more closely related to the ungulate lentiviruses, equine infectious anemia virus and visna virus, than to the primate lentiviruses, human and simian immunodeficiency viruses.
Animals↗
Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion.
Simian immunodeficiency virus (SIV) and human immunodeficiency virus share the property of tropism for CD4-bearing cells. Infection is initiated by a high-affinity interaction between CD4 and conserved domains on the viral envelope glycoprotein. In this report, we demonstrated that SIV had a restricted host range among human CD4+ cells when compared with human immunodeficiency virus type 1 or type 2. This restricted tropism was associated with the inability of the SIV envelope glycoprotein to induce membrane fusion in cells not susceptible to productive exogenous infection by SIV. We conclude that the major route of SIV entry into CD4+ cells is by envelope-mediated direct fusion with the cell and that additional envelope-cell interactions after CD4 binding are required for productive infection.
Antigens, Surface↗
Molecular cloning of feline immunodeficiency virus.
Feline immunodeficiency virus (FIV) is a T-lymphotropic retrovirus associated with immunodeficiency and opportunistic infections in cats. The discovery of FIV provides an opportunity for the development of a small animal model for AIDS. To initiate the molecular and biological characterization of FIV, cDNA clones were synthesized and used to isolate a proviral clone of FIV. Molecular cross-hybridization analysis of FIV with five lentiviruses revealed that nucleotide-sequence similarities exist between FIV and these lentiviruses in the gag-pol genes. However, nucleotide-sequence similarities were not seen upon comparison of the FIV long terminal repeat sequence with known viral sequences. Common antigenic determinants appeared to be shared by FIV, caprine arthritis encephalitis virus, and visna virus as shown by serological cross-reactivity of rabbit antibodies to caprine arthritis encephalitis virus and visna virus with the putative FIV core protein p28. These studies demonstrated that FIV is a member of the lentivirus subfamily and is distantly related to the AIDS lentiviruses of primates. Importantly, progeny virions of our molecular clone were infectious for experimentally inoculated cats. The availability of an infectious molecular clone will make possible a detailed dissection of the molecular pathogenesis of FIV, which may facilitate the development of vaccine and therapeutic strategies for AIDS.
Animals↗
Genetic diversity among simian immunodeficiency virus isolates from African green monkeys.
To characterize isolates further within the SIVagm subtype, we studied four SIVagm isolates by cross-hybridization, molecular cloning, and nucleotide sequencing. Our results indicate an unexpected degree of genetic variation among isolates within the SIVagm subtype comparable to the variation between SIVmac and HIV-2.
Animals↗
Molecular cloning of SIV from sooty mangabey monkeys.
We derived two infectious molecular clones of SIV from sooty mangabey monkeys (Cercocebus atys) and compared them by restriction enzyme mapping and limited DNA sequencing to other known primate lentiviruses. These analyses show that SIVsmm is closely related to, but distinct from, SIVmac and HIV-2. Our data suggest that SIVmac may have been derived from SIVsmm by cross-species transmission in captivity.
Amino Acid Sequence↗
Strong sequence conservation among horizontally transmissible, minimally pathogenic feline leukemia viruses.
We report the first complete nucleotide sequence (8,440 base pairs) of a biologically active feline leukemia virus (FeLV), designated FeLV-61E (or F6A), and the molecular cloning, biological activity, and env-long terminal repeat (LTR) sequence of another FeLV isolate, FeLV-3281 (or F3A). F6A corresponds to the non-disease-specific common-form component of the immunodeficiency disease-inducing strain of FeLV, FeLV-FAIDS, and was isolated from tissue DNA of a cat following experimental transmission of naturally occurring feline acquired immunodeficiency syndrome. F3A clones were derived from a subgroup-A-virus-producing feline tumor cell line. Both are unusual relative to other molecularly cloned FeLVs studied to date in their ability to induce viremia in weanling (8-week-old) cats and in their failure to induce acute disease. The F6A provirus is organized into 5'-LTR-gag-pol-env-LTR-3' regions; the gag and pol open reading frames are separated by an amber codon, and env is in a different reading frame. The deduced extracellular glycoproteins of F6A, F3A, and the Glasgow-1 subgroup A isolate of FeLV (M. Stewart, M. Warnock, A. Wheeler, N. Wilkie, J. Mullins, D. Onions, and J. Neil, J. Virol. 58:825-834, 1986) are 98% homologous, despite having been isolated from naturally infected cats 6 to 13 years apart and from widely different geographic locations. As a group, their envelope gene sequences differ markedly from those of the disease-associated subgroup B and acutely pathogenic subgroup C viruses. Thus, F6A and F3A correspond to members of a highly conserved family and represent prototypes of the horizontally transmitted, minimally pathogenic FeLV present in all naturally occurring infections.
Amino Acid Sequence↗
Serum iron, total iron binding capacity, plasma copper and hemoglobin types in anemic and poikilocytic calves.
Ninety-eight calves were studied to determine if anemia and poikilocytosis were related to iron or copper status or hemoglobin type. No significant differences were found in serum iron, total iron binding capacity, marrow iron, plasma copper or hemoglobin type between affected and normal calves. Poikilocytes were strongly inversely correlated (-0.9177) with age. Calves less than six weeks of age had more poikilocytes, lower serum iron, higher total iron binding capacity, less adult hemoglobin and more neonatal and fetal hemoglobin than calves greater than six weeks of age.
Anemia↗
Multiple cytopenias associated with monocytic proliferation in a dog.
An unusual combination of blood cytopenias and monocytic proliferation was observed in a dog. Initial hematologic findings included severe thrombocytopenia, neutropenia, mild nonregenerative anemia and apparently normal bone marrow. Subsequently, a severe persistent monocytosis developed and the bone marrow became populated with monocytes and cytophagic macrophages. Splenomegaly was due to reticuloendothelial hyperplasia and extramedultary hematopoiesis. Treatment consisted of splenectomy and azathioprine but the response was poor and the dog was euthanized. Postmortem examination revealed a hypocellular bone marrow which contained moderate numbers of monocytes and plasma cells. Neoplastic proliferation was absent in visceral organs. No definite diagnosis was established; chronic blood cell consumption, perhaps immune-mediated, may have been responsible for the extensive reticuloendothelial hyperplasia and cytophagia.
Journal Article↗
The diagnostic significance of a positive direct antiglobulin test in anemic cats.
The preparation of a feline Coombs serum (rabbit antifeline gamma globulin) is described. The direct antiglobulin test using this serum was performed on 20 anemic and 20 healthy control cats. Red cell membrane antibodies were detected in cats with feline leukemia virus infection and in others with inflammatory and neoplastic diseases. A low titre of cold agglutinating antibody was present in a high proportion of the control cats. Positive direct antiglobulin tests were noted in cats without overt hemolytic disease. It was concluded that the direct antiglobulin test in anemic cats has certain diagnostic limitations. A positive reaction should be interpreted cautiously especially when there is no clinical or laboratory evidence to support a diagnosis of autoimmune hemolytic anemia.
Anaplasmataceae Infections↗
Hereditary anomaly of neutrophil granulation in Birman cats.
A hereditary anomaly of neutrophil granulation in purebred Birman cats was described with respect to genetic, electron microscopic, histochemical, and functional characters. The trait was inherited in an autosomal recessive manner and was prevalent in the population studied. Affected cats had fine eosinophilic granules in the cytoplasm of neutrophils. The granules had normal morphology as determined by electron microscopy and did not stain for acid mucopolysaccharide. Bactericidal activity, phagocytosis, and oxidative function of affected neutrophils were not different from those of unaffected neutrophils. The anomaly was concluded to be an alteration in the content of lysosomal granules with increased affinity for acidic dyes.
Animals↗
Suppurative cholangitis in cats.
Suppurative cholangitis in 5 aged cats was characterized clinically by weight loss, depression, dehydration, icterus, and fever. The major abnormal laboratory findings were a severe left shift of WBC and a high, conjugated bilirubin concentration consistent with an inflammatory process and cholestasis. Gross pathologic findings included periductal biliary fibrosis (4 cats), periductal pancreatic fibrosis (2 cats), cholelithiasis (2 cats), deformation of the gallbladder (2 cats), and chronic interstitial pancreatitis (2 cats). Histopathologic findings in all cases were portal hepatic fibrosis, biliary hyperplasia, and suppurative exudate within dilated intrahepatic biliary ducts. Weight loss and portal fibrosis were suggestive of chronic, intermittent illness. The pathogenesis appeared to involve invasion of the bile duct by enteric bacteria. Cholangitis was observed to occur in association with pancreatitis, cholelithiasis, or anatomic abnormalities of the biliary tract.
Animals↗
A schirrhous anaplastic carcinoma in two dogs resembling mesothelioma.
The clinical, laboratory, radiographic and pathological findings of two dogs with similar neoplasms are described. Both dogs were mature males of a large breed and had pleural and abdominal effusions containing neoplastic cells. Diffuse scirrhous thickening of the pleura and serosal surfaces was a prominent feature. A fibrous layer containing nests of neoplastic, epithelial-like cells was present on serosal surfaces. The morphological appearance of the cells was suggestive of either an atypical sclerosing mesothelioma or a scirrhous carcinoma. On the basis of ultrastructural and differential staining characteristics, a diagnosis of a scirrhous carcinoma of undetermined primary origin was made in one case and of prostatic urethral origin in the other case.
Abdominal Neoplasms↗
A retrospective study of canine hemangiosarcoma and its association with acanthocytosis.
A retrospective study was conducted on cases of canine hemangiosarcoma diagnosed at the Western College of Veterinary Medicine between 1969 and 1979. A total of 33 dogs were assessed with respect to breed, age, sex and site of neoplasia. Hemangiosarcoma was most common in older dogs and there was no sex predilection. Incidence was highest in German Shepherds. The primary sites in order of most frequent occurrence were spleen, right atrium and liver. Acanthocytes were found in six of 12 dogs examined. There was no association between acanthocytosis and such factors as breed, primary site of the neoplasm and splenic or hepatic involvement.
Acanthocytes↗
Owner response to amputation of a pet's leg.
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Amputation, Surgical↗
Immunization with whole inactivated vaccine protects from infection by SIV grown in human but not macaque cells.
Homologous SIVsm stocks were generated by passage of a macaque isolate of SIVsm (SIVsm/E660) in human CEM x 174 cells or macaque peripheral blood mononuclear cells. Macaques were immunized with whole inactivated SIV vaccine consisting of virus generated by transfection of CEM x 174 cells with the SIVsmH4 clone and were challenged with either cell-free stock. Only vaccinees challenged with virus generated in human cells were protected from infection. This confirms the species-specificity of whole inactivated vaccine-mediated protection.
Animals↗
Viral genetic determinants in SIVsmmPBj pathogenesis.
A variant simian immunodeficiency virus (SIV) from sooty mangabeys, SIVsmmPBj, induces an acutely lethal disease in pigtailed macaques (Macaca nemestrina). This study further characterizes the viral genetic determinants involved in this acutely lethal disease. We have generated chimeric molecular clones constructed between SIVsmmPBj and either SIVsmH4 or SIVsmm9 to analyze the role of the 5' half of the genome and the envelope gene in the induction of acute disease. These studies suggest that the gag and gp40 of SIVsmmPBj are required for the development of lethal disease, and an additional determinant in the central regulatory gene region of the SIVsmmPBj genome is also required.
Amino Acid Sequence↗