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Increased BST2 expression during simian immunodeficiency virus infection is not a determinant of disease progression in rhesus monkeys.

Mussil B, Javed A, Töpfer K, Sauermann U, Sopper S - Retrovirology (2015)

Bottom Line: Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non-progressors (LTNPs).During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene.This association was maintained during the whole disease course.

View Article: PubMed Central - PubMed

Affiliation: Unit of Infection Models, German Primate Centre, Goettingen, Germany. bmussil@dpz.eu.

ABSTRACT

Background: Bone marrow stromal cell antigen 2 (BST2), also known as tetherin, HM1.24 or CD317 represents a type 2 integral membrane protein, which has been described to restrict the production of some enveloped viruses by inhibiting the virus release from the cell surface. This innate antiviral mechanism is counteracted by the HIV-1 viral factor Vpu, targeting BST2 for cellular degradation. Since antiviral BST2 activity has been mainly confirmed by in vitro data, we investigated its role in vivo on the disease progression using the SIV/macaque model for AIDS. We determined BST2 expression in PBMC and leukocyte subsets of uninfected and SIV-infected rhesus macaques by real-time PCR and flow cytometry and correlated it with disease progression and viral load.

Results: Compared to pre-infection levels, we found increased BST2 expression in PBMC, purified CD4(+) lymphocytes and CD14(+) monocytes of SIV-infected animals, which correlated with viral load. Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non-progressors (LTNPs). During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene. This association was maintained during the whole disease course.

Conclusion: The detected relationship between BST2 expression and viral load as well as with MX1 indicate a common regulation by the interferon response and suggest rather limited influence of BST2 in vivo on the disease outcome.

No MeSH data available.


Related in: MedlinePlus

Whole blood BST2 mRNA levels in SIV-infected macaques. BST2 mRNA levels in whole blood of 17 rhesus macaques were determined using PAXgene Blood RNA Kit and real time PCR before and at 24 weeks after infection (wpi). a BST2 mRNA levels were compared between uninfected (circles) and SIVmac251 infected animals (squares). BST2 mRNA levels are shown in copy numbers per 100 copies of GAPDH. Horizontal lines within the clusters are depicting the median. Group comparisons were calculated using two-tailed Mann–Whitney’s U test. BST2 mRNA levels at 24 wpi (b) and BST2 mRNA levels after normalization to individual pre-infection values (c) were correlated with plasma viral load. Viral load is displayed as log-transformed RNA copies per millilitre (ml) plasma. r Spearman’s correlation coefficient; regression line is shown; p, p value. Each data point represents one individual animal
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Fig1: Whole blood BST2 mRNA levels in SIV-infected macaques. BST2 mRNA levels in whole blood of 17 rhesus macaques were determined using PAXgene Blood RNA Kit and real time PCR before and at 24 weeks after infection (wpi). a BST2 mRNA levels were compared between uninfected (circles) and SIVmac251 infected animals (squares). BST2 mRNA levels are shown in copy numbers per 100 copies of GAPDH. Horizontal lines within the clusters are depicting the median. Group comparisons were calculated using two-tailed Mann–Whitney’s U test. BST2 mRNA levels at 24 wpi (b) and BST2 mRNA levels after normalization to individual pre-infection values (c) were correlated with plasma viral load. Viral load is displayed as log-transformed RNA copies per millilitre (ml) plasma. r Spearman’s correlation coefficient; regression line is shown; p, p value. Each data point represents one individual animal

Mentions: In order to investigate the impact of SIV infection on BST2 transcription, relative BST2 mRNA levels in whole blood of 17 rhesus macaques were determined before and 24 weeks after infection with SIVmac251 using an intrarectal (i.r.) repeated low dose inoculation scheme. RNA was isolated using the PAXgene Blood RNA Kit and BST2 mRNA was quantified by real time PCR relative to the housekeeping gene GAPDH. Relative BST2 mRNA levels were significantly increased after infection (Fig. 1a, p < 0.0001). Compared to individual pre-infection levels, the relative BST2 mRNA levels at 24 weeks post infection (wpi) were on average about threefold higher. Higher BST2 values in infected animals were significantly associated with higher plasma viral loads at 24 wpi (Fig. 1b, p < 0.05). Interestingly, this correlation was even better after normalizing relative BST2 mRNA expression levels to their individual pre-infection values (Fig. 1c, p < 0.01).Fig. 1


Increased BST2 expression during simian immunodeficiency virus infection is not a determinant of disease progression in rhesus monkeys.

Mussil B, Javed A, Töpfer K, Sauermann U, Sopper S - Retrovirology (2015)

Whole blood BST2 mRNA levels in SIV-infected macaques. BST2 mRNA levels in whole blood of 17 rhesus macaques were determined using PAXgene Blood RNA Kit and real time PCR before and at 24 weeks after infection (wpi). a BST2 mRNA levels were compared between uninfected (circles) and SIVmac251 infected animals (squares). BST2 mRNA levels are shown in copy numbers per 100 copies of GAPDH. Horizontal lines within the clusters are depicting the median. Group comparisons were calculated using two-tailed Mann–Whitney’s U test. BST2 mRNA levels at 24 wpi (b) and BST2 mRNA levels after normalization to individual pre-infection values (c) were correlated with plasma viral load. Viral load is displayed as log-transformed RNA copies per millilitre (ml) plasma. r Spearman’s correlation coefficient; regression line is shown; p, p value. Each data point represents one individual animal
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4641394&req=5

Fig1: Whole blood BST2 mRNA levels in SIV-infected macaques. BST2 mRNA levels in whole blood of 17 rhesus macaques were determined using PAXgene Blood RNA Kit and real time PCR before and at 24 weeks after infection (wpi). a BST2 mRNA levels were compared between uninfected (circles) and SIVmac251 infected animals (squares). BST2 mRNA levels are shown in copy numbers per 100 copies of GAPDH. Horizontal lines within the clusters are depicting the median. Group comparisons were calculated using two-tailed Mann–Whitney’s U test. BST2 mRNA levels at 24 wpi (b) and BST2 mRNA levels after normalization to individual pre-infection values (c) were correlated with plasma viral load. Viral load is displayed as log-transformed RNA copies per millilitre (ml) plasma. r Spearman’s correlation coefficient; regression line is shown; p, p value. Each data point represents one individual animal
Mentions: In order to investigate the impact of SIV infection on BST2 transcription, relative BST2 mRNA levels in whole blood of 17 rhesus macaques were determined before and 24 weeks after infection with SIVmac251 using an intrarectal (i.r.) repeated low dose inoculation scheme. RNA was isolated using the PAXgene Blood RNA Kit and BST2 mRNA was quantified by real time PCR relative to the housekeeping gene GAPDH. Relative BST2 mRNA levels were significantly increased after infection (Fig. 1a, p < 0.0001). Compared to individual pre-infection levels, the relative BST2 mRNA levels at 24 weeks post infection (wpi) were on average about threefold higher. Higher BST2 values in infected animals were significantly associated with higher plasma viral loads at 24 wpi (Fig. 1b, p < 0.05). Interestingly, this correlation was even better after normalizing relative BST2 mRNA expression levels to their individual pre-infection values (Fig. 1c, p < 0.01).Fig. 1

Bottom Line: Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non-progressors (LTNPs).During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene.This association was maintained during the whole disease course.

View Article: PubMed Central - PubMed

Affiliation: Unit of Infection Models, German Primate Centre, Goettingen, Germany. bmussil@dpz.eu.

ABSTRACT

Background: Bone marrow stromal cell antigen 2 (BST2), also known as tetherin, HM1.24 or CD317 represents a type 2 integral membrane protein, which has been described to restrict the production of some enveloped viruses by inhibiting the virus release from the cell surface. This innate antiviral mechanism is counteracted by the HIV-1 viral factor Vpu, targeting BST2 for cellular degradation. Since antiviral BST2 activity has been mainly confirmed by in vitro data, we investigated its role in vivo on the disease progression using the SIV/macaque model for AIDS. We determined BST2 expression in PBMC and leukocyte subsets of uninfected and SIV-infected rhesus macaques by real-time PCR and flow cytometry and correlated it with disease progression and viral load.

Results: Compared to pre-infection levels, we found increased BST2 expression in PBMC, purified CD4(+) lymphocytes and CD14(+) monocytes of SIV-infected animals, which correlated with viral load. Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non-progressors (LTNPs). During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene. This association was maintained during the whole disease course.

Conclusion: The detected relationship between BST2 expression and viral load as well as with MX1 indicate a common regulation by the interferon response and suggest rather limited influence of BST2 in vivo on the disease outcome.

No MeSH data available.


Related in: MedlinePlus