title: Small intestine CD4+ cell reduction and enteropathy in simian/human immunodeficiency virus KS661-infected rhesus macaques in the presence of low viral load.
abstract: Human immunodeficiency virus type 1, simian immunodeficiency virus and simian/human immunodeficiency virus (SHIV) infection generally lead to death of the host accompanied by high viraemia and profound CD4(+) T-cell depletion. SHIV clone KS661-infected rhesus macaques with a high viral load set point (HVL) ultimately experience diarrhoea and wasting at 6-12 months after infection. In contrast, infected macaques with a low viral load set point (LVL) usually live asymptomatically throughout the observation period, and are therefore referred to as asymptomatic LVL (Asym LVL) macaques. Interestingly, some LVL macaques exhibit diarrhoea and wasting similar to the symptoms of HVL macaques and are termed symptomatic LVL (Sym LVL) macaques. This study tested the hypothesis that Sym LVL macaques have the same degree of intestinal abnormalities as HVL macaques. The proviral DNA loads in lymphoid tissue and the intestines of Sym LVL and Asym LVL macaques were comparable and all infected monkeys showed villous atrophy. Notably, the CD4(+) cell frequencies of lymphoid tissues and intestines in Sym LVL macaques were remarkably lower than those in Asym LVL and uninfected macaques. Furthermore, Sym LVL and HVL macaques exhibited an increased number of activated macrophages. In conclusion, intestinal disorders including CD4(+) cell reduction and abnormal immune activation can be observed in SHIV-KS661-infected macaques independent of virus replication levels.
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Inaba
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Kenta
authors.initials: K
authors.lastname: Matsuda
authors.forename: Ai
authors.initials: A
authors.lastname: Himeno
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ibuki
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Miura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Hayami
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D019053:HIV Enteropathy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology*; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology; D011533:Proviruses / Q000302:isolation & purification; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D019562:Viral Load