title: Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6.
abstract: Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis.
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Yuki
authors: Y
authors: Ishida
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Mai
authors: M
authors: Yoneda
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Hiroyuki
authors: H
authors: Otsuki
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Yuji
authors: Y
authors: Watanabe
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Fumihiro
authors: F
authors: Kato
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Kanako
authors: K
authors: Matsuura
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Minako
authors: M
authors: Kikukawa
authors: Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research,Kumamoto University, Kumamoto 860-0811,Japan.
authors: Shuzo
authors: S
authors: Matsushita
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Takayuki
authors: T
authors: Hishiki
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Tatsuhiko
authors: T
authors: Igarashi
authors: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research,Kyoto University, 53 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507,Japan.
authors: Tomoyuki
authors: T
authors: Miura
mesh_terms: D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D006678:HIV; D006801:Humans; D008253:Macaca mulatta; D008958:Models, Molecular; D011487:Protein Conformation; D012367:RNA, Viral / Q000235:genetics; D015302:Simian Immunodeficiency Virus; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins