Experimental infection of rhesus monkeys with type D retrovirus

Journal of Virology (Impact Factor: 4.44). 12/1984; 52(2):683-6.
Source: PubMed


The naturally occurring immunodeficiency syndrome of macaque monkeys is an important animal model for the acquired immunodeficiency syndrome in humans. A new type D retrovirus, distinct from Mason-Pfizer monkey virus, has been isolated from affected animals at the New England Regional Primate Research Center. We now report the results of experimental infection of macaques with retrovirus D/New England after 13 months of study. Inoculated macaques developed lymphadenopathy without follicular hyperplasia, profound neutropenia, and a transient decrease in peripheral blood lymphocyte blastogenic responsiveness. Despite our varying the strain of virus, the manner in which the virus was grown, the size of the inoculum, and the age of the inoculated animals, infected macaques have not developed opportunistic infections or profound, prolonged loss of T cell function, key features of the macaque immunodeficiency syndrome. Therefore, experimental infection of naive macaques with D/New England has not reproduced the naturally occurring macaque immunodeficiency syndrome.

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Available from: Kristine Holley, Oct 06, 2015
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    • "Such differences seem to depend on the virus subtype and the macaque species of the infected host. The SRV-1 isolate D1/RHE/CA, for example, was significantly more pathogenic in rhesus macaques than the D1/CYC/NE isolate [18,19], and differences in cell tropisms as a possible cause for such varying pathogenicity have been identified [20,21]. The SRV-2 isolate, D2/CEL/OR, caused severe immunodeficiency in Celebes black macaques but did not cause any symptoms when transmitted to rhesus macaques [13]. "
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    ABSTRACT: D-type simian retrovirus-2 (SRV-2) causes an AIDS-like immune deficiency syndrome (SAIDS) in various macaque species. SAIDS is often accompanied by retroperitoneal fibromatosis (RF), an aggressive fibroproliferative disorder reminiscent of Kaposi's sarcoma in patients with HIV-induced AIDS. In order to determine the association of SRV-2 subtypes with SAIDS-RF, and study the evolution and transmission of SRV-2 in captive macaque populations, we have molecularly characterized the env gene of a number of SRV-2 isolates from different macaque species with and without RF. We sequenced the env gene from eighteen SRV-2 isolates and performed sequence comparisons and phylogenetic analyses. Our studies revealed the presence of six distinct subtypes of SRV-2, three of which were associated with SAIDS-RF cases. We found no association between SRV-2 subtypes and a particular macaque species. Little sequence variation was detected in SRV-2 isolates from the same individual, even after many years of infection, or from macaques housed together or related by descent from a common infected parent. Seventy-two amino acid changes were identified, most occurring in the larger gp70 surface protein subunit. In contrast to the lentiviruses, none of the amino acid variations involved potential N-linked glycosylation sites. Structural analysis of a domain within the gp22/gp20 transmembrane subunit that was 100% conserved between SRV-2 subtypes, revealed strong similarities to a disulfide-bonded loop that is crucial for virus-cell fusion and is found in retroviruses and filoviruses. Our study suggests that separate introductions of at least six parental SRV-2 subtypes into the captive macaque populations in the U.S. have occurred with subsequent horizontal transfer between macaque species and primate centers. No specific association of a single SRV-2 subtype with SAIDS-RF was seen. The minimal genetic variability of the env gene within a subtype over time suggests that a strong degree of adaptation to its primate host has occurred during evolution of the virus.
    Virology Journal 02/2006; 3:11. DOI:10.1186/1743-422X-3-11 · 2.18 Impact Factor
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    ABSTRACT: We haveisolated a molecular cloneofthefull-length integrated provirus ofsimianacquired immune deficiency syndrome retrovirus serotype 1(SRV-1) froma fatal caseofsimianacquired immunedeficiency syndrome inajuvenile rhesus macaque.An integrated SRV-1provirus was cloned, sequenced, andfoundto contain fourlarge openreading framesencoding gag-precursorprotein, protease, polymerase, andenvelope. Theproviral clone was transfected intoD17canine osteosarcoma cells andfoundtoproduce infectious virus. A comparison ofthesequencesofthisclone witha noninfectious cloneshowed20differences, resulting in10 aminoacidchanges. Also, a cluster ofexchanges, shortinsertions, anddeletions inthe5'leader sequences resulted inextension ofthetRNALYSprimer-binding sitefrom14to19nucleotides. Virusisolated from transfected cells was showntobeinfectious andpathogenic, resulting indisease thatfollowed thesame time courseandmortality asdisease induced byuncloned, invitro cultivated virus isolated fromdiseased animals. Theseresults unequivocally showthat atypeD retrovirus (SRV-1) causesafatal immunosuppressive syndrome inrhesus monkeys. A typeD retrovirus, simian acquired immunedeficiency syndrome (SAIDS) retrovirus serotype 1(SRV-1), hascon- sistently beenassociated withSAIDSoccurring spontane- ously inrhesus monkeys (Macacca mulatta) attheCalifornia Primate Research Center (19, 20,21). Thisfatal immunosup- pressive disease wasexperimentally transmitted torhesus monkeyswithtissue culture-derived virus. Animals with terminal disease hadavariety ofclinical signs ofSAIDS,
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