TY - JOUR
T1 - A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture
AU - Iwanami, Shoya
AU - Kakizoe, Yusuke
AU - Morita, Satoru
AU - Miura, Tomoyuki
AU - Nakaoka, Shinji
AU - Iwami, Shingo
N1 - Funding Information:
This work was supported in part by the JSPS Research Fellowship for Young Scientists Grant Number 16 J03672 (to Y.K.); the Japan Science and Technology Agency (JST) PRESTO program (to S.N. and S.I.); JST RISTEX program (to S.I.); JST CREST program (to S.I.); the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers 26400388 (to S.M.); 16H04682 (to T.M.); 15KT0147, 15H05707, and 16 K05265 (to S.N.); 15KT0107, 26287025, 16KT0111, 16H04845, and 16 K13777 (to S.I.); the Japan Agency for Medical Research and Development, AMED, Grant Numbers 16fk0410102h0001, 16fk0410201h0102, 16fk0410208h0002, and 15fk0410014h0001 (to T.M.); 16fk0108316h0003 (to S.I.); Mitsui Life Social Welfare Foundation (to. S.I.); The Shin-Nihon of Advanced Medical Research (to S.I.); GSK Japan Research Grant 2016 (to S.I.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/4/21
Y1 - 2017/4/21
N2 - Background: The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains - the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64 - and measured the time-course of experimental data in cell culture. Methods: We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains. Results and conclusions: We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID50, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID50/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture.
AB - Background: The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains - the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64 - and measured the time-course of experimental data in cell culture. Methods: We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains. Results and conclusions: We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID50, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID50/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture.
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U2 - 10.1186/s12976-017-0055-8
DO - 10.1186/s12976-017-0055-8
M3 - Article
C2 - 28431573
AN - SCOPUS:85018468521
SN - 1742-4682
VL - 14
JO - Theoretical Biology and Medical Modelling
JF - Theoretical Biology and Medical Modelling
IS - 1
M1 - 9
ER -
