TY - JOUR
T1 - Genetic similarity of circulating and small intestinal virus at the end stage of acute pathogenic simian-human immunodeficiency virus infection
AU - Matsuyama-Murata, Megumi
AU - Inaba, Katsuhisa
AU - Horiuchi, Reii
AU - Fukazawa, Yoshinori
AU - Ibuki, Kentaro
AU - Hayami, Masanori
AU - Miura, Tomoyuki
PY - 2013
Y1 - 2013
N2 - To understand the pathogenicity of acquired immune deficiency syndrome (AIDS), it is important to clarify where, when and how the virus replicates in the body of infected individuals. To identify the major virus replication site at the end stage of SHIV infection, we investigated the systemic tissues of SHIV-infected monkeys that developed AIDS-like disease. We quantified proviral DNA, and compared the mutation patterns of the viruses in various systemic tissues and in peripheral blood through phylogenetic analysis of the full genome sequence. We found that the amounts of proviral DNA detected in internal tissues were higher than those in peripheral blood mononuclear cells. In the sequence and phylogenetic tree analyses, the mutation patterns of the viruses in each tissue were generally different. However, the mutation pattern of the viruses in the jejunum and mesenteric lymph node were most similar to that of plasma viral RNA among the tissues examined in all three monkeys. In two of the three monkeys, which were euthanized earlier, viruses in the jejunum and mesenteric lymph node occupied the root position of the phylogenetic tree. Furthermore, in these tissues, more than 50% of SHIV-expressing cells were identified as macrophages based on co-expression of CD68. These results suggest that macrophages of the small intestine and/or mesenteric lymph node are the major virus production site at the end stage of SHIV infection of macaques.
AB - To understand the pathogenicity of acquired immune deficiency syndrome (AIDS), it is important to clarify where, when and how the virus replicates in the body of infected individuals. To identify the major virus replication site at the end stage of SHIV infection, we investigated the systemic tissues of SHIV-infected monkeys that developed AIDS-like disease. We quantified proviral DNA, and compared the mutation patterns of the viruses in various systemic tissues and in peripheral blood through phylogenetic analysis of the full genome sequence. We found that the amounts of proviral DNA detected in internal tissues were higher than those in peripheral blood mononuclear cells. In the sequence and phylogenetic tree analyses, the mutation patterns of the viruses in each tissue were generally different. However, the mutation pattern of the viruses in the jejunum and mesenteric lymph node were most similar to that of plasma viral RNA among the tissues examined in all three monkeys. In two of the three monkeys, which were euthanized earlier, viruses in the jejunum and mesenteric lymph node occupied the root position of the phylogenetic tree. Furthermore, in these tissues, more than 50% of SHIV-expressing cells were identified as macrophages based on co-expression of CD68. These results suggest that macrophages of the small intestine and/or mesenteric lymph node are the major virus production site at the end stage of SHIV infection of macaques.
KW - AIDS
KW - Evolution
KW - Hiv
KW - Immunohistochemistry
KW - Phylogenesis
KW - Rhesus
KW - Shiv
KW - Siv
UR - http://www.scopus.com/inward/record.url?scp=84885346904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885346904&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2013.00204
DO - 10.3389/fmicb.2013.00204
M3 - Article
C2 - 23885255
AN - SCOPUS:84885346904
SN - 1664-302X
VL - 4
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
IS - JUL
ER -