BACKGROUND: Although virus-specific CD4(+) T lymphocytes emerge rapidly during primary cytomegalovirus (CMV) infection in humans, they exhibit a state of prolonged functional exhaustion of unknown etiology. To investigate the suitability of rhesus macaques as a model of primary human CMV infection, we examined the virologic and immunologic features of naturally acquired primary CMV infection in rhesus macaques. METHODS: CMV-specific CD4(+) T lymphocytes and CMV load in blood, saliva, and urine were evaluated in a cohort of simian immunodeficiency virus (SIV)-negative rhesus macaques stratified by age into infant, juvenile, and adult groups. RESULTS: CMV infection was detected in juvenile and adult monkeys but not in infant monkeys. CMV loads and shedding frequency in urine and saliva were significantly higher in the 2-3-year old juvenile monkeys, compared with the adult monkeys. The increased CMV load in juvenile monkeys was associated with lower polyfunctionality, impaired proliferation, and increased expression of the inhibitory receptor PD-1 in CMV-specific CD4(+) T lymphocytes. The proliferative defect was partially reversible by exogenous PD-1 blockade or addition of interleukin 2. CONCLUSIONS: Postnatal acquisition of primary CMV infection in rhesus macaques results in prolonged virus excretion and impaired CMV-specific CD4(+) T-lymphocyte function, findings that recapitulate key features of primary CMV infection in humans.
BACKGROUND: Although virus-specific CD4(+) T lymphocytes emerge rapidly during primary cytomegalovirus (CMV) infection in humans, they exhibit a state of prolonged functional exhaustion of unknown etiology. To investigate the suitability of rhesus macaques as a model of primary humanCMV infection, we examined the virologic and immunologic features of naturally acquired primary CMV infection in rhesus macaques. METHODS: CMV-specific CD4(+) T lymphocytes and CMV load in blood, saliva, and urine were evaluated in a cohort of simian immunodeficiency virus (SIV)-negative rhesus macaques stratified by age into infant, juvenile, and adult groups. RESULTS:CMV infection was detected in juvenile and adult monkeys but not in infant monkeys. CMV loads and shedding frequency in urine and saliva were significantly higher in the 2-3-year old juvenile monkeys, compared with the adult monkeys. The increased CMV load in juvenile monkeys was associated with lower polyfunctionality, impaired proliferation, and increased expression of the inhibitory receptor PD-1 in CMV-specific CD4(+) T lymphocytes. The proliferative defect was partially reversible by exogenous PD-1 blockade or addition of interleukin 2. CONCLUSIONS: Postnatal acquisition of primary CMV infection in rhesus macaques results in prolonged virus excretion and impaired CMV-specific CD4(+) T-lymphocyte function, findings that recapitulate key features of primary CMV infection in humans.
Authors: Christine J Pitcher; Shoko I Hagen; Joshua M Walker; Richard Lum; Bridget L Mitchell; Vernon C Maino; Michael K Axthelm; Louis J Picker Journal: J Immunol Date: 2002-01-01 Impact factor: 5.422
Authors: Amitinder Kaur; Corrina L Hale; Bradley Noren; Nadine Kassis; Meredith A Simon; R Paul Johnson Journal: J Virol Date: 2002-04 Impact factor: 5.103
Authors: Laila E Gamadia; Ester B M Remmerswaal; Jan F Weel; Frederieke Bemelman; René A W van Lier; Ineke J M Ten Berge Journal: Blood Date: 2002-10-31 Impact factor: 22.113
Authors: Victor Appay; John J Zaunders; Laura Papagno; Julian Sutton; Angel Jaramillo; Anele Waters; Philippa Easterbrook; Pat Grey; Don Smith; Andrew J McMichael; David A Cooper; Sarah L Rowland-Jones; Anthony D Kelleher Journal: J Immunol Date: 2002-06-01 Impact factor: 5.422
Authors: Amitinder Kaur; Nadine Kassis; Corrina L Hale; Meredith Simon; Michelle Elliott; Alicia Gomez-Yafal; Jeffrey D Lifson; Ronald C Desrosiers; Fred Wang; Peter Barry; Michael Mach; R Paul Johnson Journal: J Virol Date: 2003-05 Impact factor: 5.103
Authors: Julie R Brahmer; Scott S Tykodi; Laura Q M Chow; Wen-Jen Hwu; Suzanne L Topalian; Patrick Hwu; Charles G Drake; Luis H Camacho; John Kauh; Kunle Odunsi; Henry C Pitot; Omid Hamid; Shailender Bhatia; Renato Martins; Keith Eaton; Shuming Chen; Theresa M Salay; Suresh Alaparthy; Joseph F Grosso; Alan J Korman; Susan M Parker; Shruti Agrawal; Stacie M Goldberg; Drew M Pardoll; Ashok Gupta; Jon M Wigginton Journal: N Engl J Med Date: 2012-06-02 Impact factor: 91.245
Authors: Kristy M Bialas; Takayuki Tanaka; Dollnovan Tran; Valerie Varner; Eduardo Cisneros De La Rosa; Flavia Chiuppesi; Felix Wussow; Lisa Kattenhorn; Sheila Macri; Erika L Kunz; Judy A Estroff; Jennifer Kirchherr; Yujuan Yue; Qihua Fan; Michael Lauck; David H O'Connor; Allison H S Hall; Alvarez Xavier; Don J Diamond; Peter A Barry; Amitinder Kaur; Sallie R Permar Journal: Proc Natl Acad Sci U S A Date: 2015-10-19 Impact factor: 11.205
Authors: C Fornara; F Zavaglio; M Furione; A Sarasini; P d'Angelo; A Arossa; A Spinillo; D Lilleri; F Baldanti Journal: Med Microbiol Immunol Date: 2022-08-12 Impact factor: 4.148
Authors: Husam Taher; Eisa Mahyari; Craig Kreklywich; Luke S Uebelhoer; Matthew R McArdle; Matilda J Moström; Amruta Bhusari; Michael Nekorchuk; Xiaofei E; Travis Whitmer; Elizabeth A Scheef; Lesli M Sprehe; Dawn L Roberts; Colette M Hughes; Kerianne A Jackson; Andrea N Selseth; Abigail B Ventura; Hillary C Cleveland-Rubeor; Yujuan Yue; Kimberli A Schmidt; Jason Shao; Paul T Edlefsen; Jeremy Smedley; Timothy F Kowalik; Richard J Stanton; Michael K Axthelm; Jacob D Estes; Scott G Hansen; Amitinder Kaur; Peter A Barry; Benjamin N Bimber; Louis J Picker; Daniel N Streblow; Klaus Früh; Daniel Malouli Journal: PLoS Pathog Date: 2020-11-24 Impact factor: 7.464
Authors: Michael J Cannon; Jennifer D Stowell; Rebekah Clark; Philip R Dollard; Delaney Johnson; Karen Mask; Cynthia Stover; Karen Wu; Minal Amin; Will Hendley; Jing Guo; D Scott Schmid; Sheila C Dollard Journal: BMC Infect Dis Date: 2014-11-13 Impact factor: 3.090