Generation of the pathogenic R5-tropic simian/human immunodeficiency virus SHIVAD8 by serial passaging in rhesus macaques. 2010

Yoshiaki Nishimura, and Masashi Shingai, and Ronald Willey, and Reza Sadjadpour, and Wendy R Lee, and Charles R Brown, and Jason M Brenchley, and Alicia Buckler-White, and Rahel Petros, and Michael Eckhaus, and Victoria Hoffman, and Tatsuhiko Igarashi, and Malcolm A Martin
Laboratory of Molecular Microbiology, National Institutes of Health, Bethesda, MD 20892-0460, USA.

A new pathogenic R5-tropic simian/human immunodeficiency virus (SHIV) was generated following serial passaging in rhesus macaques. All 13 animals inoculated with SHIV(AD8) passaged lineages experienced marked depletions of CD4(+) T cells. Ten of these infected monkeys became normal progressors (NPs) and had gradual losses of both memory and naïve CD4(+) T lymphocytes, generated antiviral CD4(+) and CD8(+) T cell responses, and sustained chronic immune activation while maintaining variable levels of plasma viremia (10(2) to 10(5) RNA copies/ml for up to 3 years postinfection [p.i.]). To date, five NPs developed AIDS associated with opportunistic infections caused by Pneumocystis carinii, Mycobacterium avium, and Campylobacter coli that required euthanasia between weeks 100 and 199 p.i. Three other NPs have experienced marked depletions of circulating CD4(+) T lymphocytes (92 to 154 cells/microl) following 1 to 2 years of infection. When tested for coreceptor usage, the viruses isolated from four NPs at the time of their euthanasia remained R5 tropic. Three of the 13 SHIV(AD8)-inoculated macaques experienced a rapid-progressor syndrome characterized by sustained plasma viremia of >1 x 10(7) RNA copies/ml and rapid irreversible loss of memory CD4(+) T cells that required euthanasia between weeks 19 and 23 postinfection. The sustained viremia, associated depletion of CD4(+) T lymphocytes, and induction of AIDS make the SHIV(AD8) lineage of viruses a potentially valuable reagent for vaccine studies.

UI MeSH Term Description Entries
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D009162 Mycobacterium avium A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans.
D011991 Receptors, Virus Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response. Viral Entry Receptor,Viral Entry Receptors,Virus Attachment Factor,Virus Attachment Factors,Virus Attachment Receptor,Virus Attachment Receptors,Virus Entry Receptor,Virus Entry Receptors,Virus Receptor,Virus Receptors,Attachment Factor, Virus,Attachment Factors, Virus,Attachment Receptor, Virus,Attachment Receptors, Virus,Entry Receptor, Viral,Entry Receptor, Virus,Entry Receptors, Viral,Entry Receptors, Virus,Receptor, Viral Entry,Receptor, Virus,Receptor, Virus Attachment,Receptor, Virus Entry,Receptors, Viral Entry,Receptors, Virus Attachment,Receptors, Virus Entry
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012692 Serial Passage Inoculation of a series of animals or in vitro tissue with an infectious bacterium or virus, as in VIRULENCE studies and the development of vaccines. Passage, Serial,Passages, Serial,Serial Passages
D014766 Viremia The presence of viruses in the blood. Viremias
D015302 Simian Immunodeficiency Virus Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV. SIV (Simian immunodeficiency virus),Immunodeficiency Viruses, Simian,Simian Immunodeficiency Viruses,Immunodeficiency Virus, Simian
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016097 Simian Acquired Immunodeficiency Syndrome Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS. AIDS, Simian,SAIDS,Simian AIDS,Simian Acquired Immune Deficiency Syndrome,Simian Acquired Immuno-Deficiency Syndrome,AIDSs, Simian,Simian AIDSs,Simian Acquired Immuno Deficiency Syndrome
D017000 Campylobacter coli A species of gram-negative, rod-shaped bacteria isolated from the intestinal tract of swine, poultry, and man. It may be pathogenic. Vibrio coli

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