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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 (pā€Š=ā€Š0.002). 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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Comparison of the replication kinetics of different HIV-1 isolates from patients infected with CRF07_BC or subtype B (A and B) as well as recombinant HIV-1 virus with or without a 7 amino-acid deletion in the p6gag protein.(A) PBMCs were infected with fixed amounts of different HIV-1 subtype B (square) or CRF07_BC (circle) isolates and cultural supernatants were collected at days 4, 7, 11, 14, 18 and 21 post-infection. (B) The representative replicative curves of CRF07_BC and subtype B isolates deduced from Fig. 2A. (C) MT2 cells were infected with wild type (wt) or recombinant mutant virus with a 7 amino-acid deletion at the p6gag (7d). Supernatants were collected at days 2, 4, 6, 8, 10, 12, and 14 post-infection. Viral replication was monitored through p24 antigen production. One-way analysis of variance (ANOVA) and Tukey's post hoc test were used to estimate the differences between subtypes, or between the recombinant viruses.
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pone-0114441-g002: Comparison of the replication kinetics of different HIV-1 isolates from patients infected with CRF07_BC or subtype B (A and B) as well as recombinant HIV-1 virus with or without a 7 amino-acid deletion in the p6gag protein.(A) PBMCs were infected with fixed amounts of different HIV-1 subtype B (square) or CRF07_BC (circle) isolates and cultural supernatants were collected at days 4, 7, 11, 14, 18 and 21 post-infection. (B) The representative replicative curves of CRF07_BC and subtype B isolates deduced from Fig. 2A. (C) MT2 cells were infected with wild type (wt) or recombinant mutant virus with a 7 amino-acid deletion at the p6gag (7d). Supernatants were collected at days 2, 4, 6, 8, 10, 12, and 14 post-infection. Viral replication was monitored through p24 antigen production. One-way analysis of variance (ANOVA) and Tukey's post hoc test were used to estimate the differences between subtypes, or between the recombinant viruses.

Mentions: To confirm the findings mentioned above, we used co-culture methods to isolate CRF07_BC and subtype B strains from clinical specimens to compare their replication capacity. The results showed that the replication capacity of 9 CRF07_BC isolates was relatively lower than that of the 4 subtype B isolates (Fig. 2A). As shown in Fig. 2B, CRF07_BC isolates had significantly lower replication capacity than subtype B isolates.


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)

Comparison of the replication kinetics of different HIV-1 isolates from patients infected with CRF07_BC or subtype B (A and B) as well as recombinant HIV-1 virus with or without a 7 amino-acid deletion in the p6gag protein.(A) PBMCs were infected with fixed amounts of different HIV-1 subtype B (square) or CRF07_BC (circle) isolates and cultural supernatants were collected at days 4, 7, 11, 14, 18 and 21 post-infection. (B) The representative replicative curves of CRF07_BC and subtype B isolates deduced from Fig. 2A. (C) MT2 cells were infected with wild type (wt) or recombinant mutant virus with a 7 amino-acid deletion at the p6gag (7d). Supernatants were collected at days 2, 4, 6, 8, 10, 12, and 14 post-infection. Viral replication was monitored through p24 antigen production. One-way analysis of variance (ANOVA) and Tukey's post hoc test were used to estimate the differences between subtypes, or between the recombinant viruses.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114441-g002: Comparison of the replication kinetics of different HIV-1 isolates from patients infected with CRF07_BC or subtype B (A and B) as well as recombinant HIV-1 virus with or without a 7 amino-acid deletion in the p6gag protein.(A) PBMCs were infected with fixed amounts of different HIV-1 subtype B (square) or CRF07_BC (circle) isolates and cultural supernatants were collected at days 4, 7, 11, 14, 18 and 21 post-infection. (B) The representative replicative curves of CRF07_BC and subtype B isolates deduced from Fig. 2A. (C) MT2 cells were infected with wild type (wt) or recombinant mutant virus with a 7 amino-acid deletion at the p6gag (7d). Supernatants were collected at days 2, 4, 6, 8, 10, 12, and 14 post-infection. Viral replication was monitored through p24 antigen production. One-way analysis of variance (ANOVA) and Tukey's post hoc test were used to estimate the differences between subtypes, or between the recombinant viruses.
Mentions: To confirm the findings mentioned above, we used co-culture methods to isolate CRF07_BC and subtype B strains from clinical specimens to compare their replication capacity. The results showed that the replication capacity of 9 CRF07_BC isolates was relatively lower than that of the 4 subtype B isolates (Fig. 2A). As shown in Fig. 2B, CRF07_BC isolates had significantly lower replication capacity than subtype B isolates.

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 (pā€Š=ā€Š0.002). 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