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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.

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 YM - PLoS ONE (2014)

Bottom Line: 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.The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.

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.

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Comparisons of the changes of CD4 cell count and HIV-1 viral loads after the first clinical visit among the following four groups of treatment naïve patients.Men who have sex with men (MSM, 357 patients for CD4 cell count and 371 patients for viral loads analysis) vs. injection drug users (IDUs, 129 patients for CD4 cell count and 128 patients for viral loads analysis) (Fig. 1A and 1B); patients infected with CRF07_BC vs. infected with subtype B (Figs. 1C and 1D). A generalized estimating equation model was used for the analyses.
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pone-0114441-g001: Comparisons of the changes of CD4 cell count and HIV-1 viral loads after the first clinical visit among the following four groups of treatment naïve patients.Men who have sex with men (MSM, 357 patients for CD4 cell count and 371 patients for viral loads analysis) vs. injection drug users (IDUs, 129 patients for CD4 cell count and 128 patients for viral loads analysis) (Fig. 1A and 1B); patients infected with CRF07_BC vs. infected with subtype B (Figs. 1C and 1D). A generalized estimating equation model was used for the analyses.

Mentions: As shown in Figs. 1A and 1B, compared with MSM, IDUs had consistently higher CD4 cell count and lower HIV-1 viral loads over 2.5 years. A GEE model was used to identify factors associated with changes of CD4 cell count or viral loads. The variables which potentially may influence the CD4 cell count or HIV-1 viral loads were considered in this analysis. As shown in Table 3, regardless of whether “mode of infection” was added in the model (multivariate model I vs. model II), factors significantly associated with CD4 cell count changes included older age, subtypes (CRF01_AE and CRF08_BC), higher viral loads and no previous HAART. In contrast, when we analyzed factors associated with changes of viral loads, once we deleted “mode of infection” from the model (multivariate model II), we found that CRF07_BC infection became significantly associated with lower viral loads compared to subtype B infection (Table 4).


Patients infected with CRF07_BC have significantly lower viral loads than patients with HIV-1 subtype B: mechanism and impact on disease progression.

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 YM - PLoS ONE (2014)

Comparisons of the changes of CD4 cell count and HIV-1 viral loads after the first clinical visit among the following four groups of treatment naïve patients.Men who have sex with men (MSM, 357 patients for CD4 cell count and 371 patients for viral loads analysis) vs. injection drug users (IDUs, 129 patients for CD4 cell count and 128 patients for viral loads analysis) (Fig. 1A and 1B); patients infected with CRF07_BC vs. infected with subtype B (Figs. 1C and 1D). A generalized estimating equation model was used for the analyses.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263662&req=5

pone-0114441-g001: Comparisons of the changes of CD4 cell count and HIV-1 viral loads after the first clinical visit among the following four groups of treatment naïve patients.Men who have sex with men (MSM, 357 patients for CD4 cell count and 371 patients for viral loads analysis) vs. injection drug users (IDUs, 129 patients for CD4 cell count and 128 patients for viral loads analysis) (Fig. 1A and 1B); patients infected with CRF07_BC vs. infected with subtype B (Figs. 1C and 1D). A generalized estimating equation model was used for the analyses.
Mentions: As shown in Figs. 1A and 1B, compared with MSM, IDUs had consistently higher CD4 cell count and lower HIV-1 viral loads over 2.5 years. A GEE model was used to identify factors associated with changes of CD4 cell count or viral loads. The variables which potentially may influence the CD4 cell count or HIV-1 viral loads were considered in this analysis. As shown in Table 3, regardless of whether “mode of infection” was added in the model (multivariate model I vs. model II), factors significantly associated with CD4 cell count changes included older age, subtypes (CRF01_AE and CRF08_BC), higher viral loads and no previous HAART. In contrast, when we analyzed factors associated with changes of viral loads, once we deleted “mode of infection” from the model (multivariate model II), we found that CRF07_BC infection became significantly associated with lower viral loads compared to subtype B infection (Table 4).

Bottom Line: 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.The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.

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.

Show MeSH
Related in: MedlinePlus