Mucosal simian immunodeficiency virus transmission in African green monkeys: susceptibility to infection is proportional to target cell availability at mucosal sites.
African green monkeys (AGMs) are naturally infected with a simian immunodeficiency virus (SIVagm) that is nonpathogenic in its host. Although SIVagm is common and widespread, little is known about the mechanisms that govern its transmission. Since the earliest virus-host interactions may provide key insights into the nonpathogenic phenotype of SIVagm, we developed a mucosal transmission model for this virus. Using plasma from an acutely infected AGM as the virus inoculum, we exposed adult and juvenile AGMs, as well as pigtailed macaques (PTMs) as a nonnatural host control, by mucosal routes to increasing titers of virus and compared the doses needed to establish a productive infection. Four juvenile and four adult AGMs as well as two PTMs were intrarectally (IR) exposed, while two additional adult female AGMs were intravaginally (IVAG) exposed. No animal became infected following exposure to 10(5) RNA copies. Both PTMs but none of the AGMs became infected following exposure to 10(6) RNA copies. Finally, all adult AGMs and two of the four juvenile AGMs became infected following exposure to 10(7) RNA copies, acquiring either one (2 IR infected juveniles, 1 IR infected adult, 2 IVAG infected adults) or two (3 IR infected adults) transmitted founder viruses. These results were consistent with immunophenotypic data, which revealed a significant correlation between the percentage of CD4(+) T cells expressing CCR5 in the mucosa and the susceptibility to infection, in terms of both the viral dose and the numbers of transmitted founder viruses. Moreover, studies of uninfected AGMs showed that the fraction of CCR5-expressing CD4(+) T cells increased significantly with age. These results indicate that (i) AGMs are readily infected with SIVagm by both intrarectal and intravaginal routes, (ii) susceptibility to infection is proportional to the number of available CCR5(+) CD4(+) target cells in the mucosa, and (iii) the paucity of CCR5(+) CD4(+) target cells in infant and juvenile AGMs may explain the near absence of vertical transmission.
Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
Ivona
I
Pandrea
Nicholas F
NF
Parrish
Kevin
K
Raehtz
Thaidra
T
Gaufin
Hannah J
HJ
Barbian
Dongzhu
D
Ma
Jan
J
Kristoff
Rajeev
R
Gautam
Fang
F
Zhong
George S
GS
Haret-Richter
Anita
A
Trichel
George M
GM
Shaw
Beatrice H
BH
Hahn
Cristian
C
Apetrei
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops; D004198:Disease Susceptibility / Q000276:immunology; D019143:Evolution, Molecular; D005260:Female; D008254:Macaca nemestrina; D008297:Male; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology*; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics
D019713:Receptors, CCR5; D014759:Viral Envelope Proteins