Patients infected with CRF07-BC have significantly lower viral loads than patients with HIV-1 subtype B: Mechanism and impact on disease progression

Szu Wei Huang; Sheng Fan Wang; Yu Ting Lin; Chia Hung Yen; Chih Hao Lee; Wing Wai Wong; Hung Chin Tsai; Chia Jui Yang; Bor Shen Hu; Yu Huei Lin; Chin Tien Wang; Jaang Jiun Wang; Zixin Hu; Daniel R. Kuritzkes; Yen Hsu Chen; Yi Ming Arthur Chen

doi:10.1371/journal.pone.0114441

Patients infected with CRF07-BC have significantly lower viral loads than patients with HIV-1 subtype B: Mechanism and impact on disease progression

Szu Wei Huang, Sheng Fan Wang, Yu Ting Lin, Chia Hung Yen, Chih Hao Lee, Wing Wai Wong, Hung Chin Tsai, Chia Jui Yang, Bor Shen Hu, Yu Huei Lin, Chin Tien Wang, Jaang Jiun Wang, Zixin Hu, Daniel R. Kuritzkes, Yen Hsu Chen, Yi Ming Arthur Chen

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Abstract

The circulating recombinant form (CRF) 07-BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6^gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07-BC and to elucidate its mechanism. Twenty-one patients infected with CRF07-BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07-BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p=0.002). The replicative capacity of nine CRF07-BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6^gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6^gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07-BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6^gag.

Original language	English
Article number	e114441
Journal	PLoS One
Volume	9
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0114441
Publication status	Published - Dec 11 2014
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0114441

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Huang, S. W., Wang, S. F., Lin, Y. T., Yen, C. H., Lee, C. H., Wong, W. W., Tsai, H. C., Yang, C. J., Hu, B. S., Lin, Y. H., Wang, C. T., Wang, J. J., Hu, Z., Kuritzkes, D. R., Chen, Y. H., & Chen, Y. M. A. (2014). Patients infected with CRF07-BC have significantly lower viral loads than patients with HIV-1 subtype B: Mechanism and impact on disease progression. PLoS One, 9(12), Article e114441. https://doi.org/10.1371/journal.pone.0114441

Huang, SW, Wang, SF, Lin, YT, Yen, CH, Lee, CH, Wong, WW, Tsai, HC, Yang, CJ, Hu, BS, Lin, YH, Wang, CT, Wang, JJ, Hu, Z, Kuritzkes, DR, Chen, YH & Chen, YMA 2014, 'Patients infected with CRF07-BC have significantly lower viral loads than patients with HIV-1 subtype B: Mechanism and impact on disease progression', PLoS One, vol. 9, no. 12, e114441. https://doi.org/10.1371/journal.pone.0114441

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title = "Patients infected with CRF07-BC have significantly lower viral loads than patients with HIV-1 subtype B: Mechanism and impact on disease progression",

abstract = "The circulating recombinant form (CRF) 07-BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07-BC and to elucidate its mechanism. Twenty-one patients infected with CRF07-BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07-BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p=0.002). The replicative capacity of nine CRF07-BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07-BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.",

author = "Huang, {Szu Wei} and Wang, {Sheng Fan} and Lin, {Yu Ting} and Yen, {Chia Hung} and Lee, {Chih Hao} and Wong, {Wing Wai} and Tsai, {Hung Chin} and Yang, {Chia Jui} and Hu, {Bor Shen} and Lin, {Yu Huei} and Wang, {Chin Tien} and Wang, {Jaang Jiun} and Zixin Hu and Kuritzkes, {Daniel R.} and Chen, {Yen Hsu} and Chen, {Yi Ming Arthur}",

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T1 - Patients infected with CRF07-BC have significantly lower viral loads than patients with HIV-1 subtype B

T2 - Mechanism and impact on disease progression

AU - Huang, Szu Wei

AU - Wang, Sheng Fan

AU - Lin, Yu Ting

AU - Yen, Chia Hung

AU - Lee, Chih Hao

AU - Wong, Wing Wai

AU - Tsai, Hung Chin

AU - Yang, Chia Jui

AU - Hu, Bor Shen

AU - Lin, Yu Huei

AU - Wang, Chin Tien

AU - Wang, Jaang Jiun

AU - Hu, Zixin

AU - Kuritzkes, Daniel R.

AU - Chen, Yen Hsu

AU - Chen, Yi Ming Arthur

PY - 2014/12/11

Y1 - 2014/12/11

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Patients infected with CRF07-BC have significantly lower viral loads than patients with HIV-1 subtype B: Mechanism and impact on disease progression

Abstract

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UN SDGs

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