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Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

Cánepa C, Salido J, Ruggieri M, Fraile S, Pataccini G, Berini C, Biglione M - Viruses (2015)

Bottom Line: Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003) was observed.Age and sex were associated with PVL in G1 and G2, respectively.Mutations in the distal and central regions of Tax Responsive Elements (TRE) 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03). indeterminate WB results confirmed later as HTLV-1 positive may be associated with low PVL levels.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. canepa.camila@gmail.com.

ABSTRACT

Background: indeterminate Western blot (WB) patterns are a major concern for diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) infection, even in non-endemic areas.

Objectives: (a) to define the prevalence of indeterminate WB among different populations from Argentina; (b) to evaluate if low proviral load (PVL) is associated with indeterminate WB profiles; and (c) to describe mutations in LTR and tax sequence of these cases.

Results: Among 2031 samples, 294 were reactive by screening. Of them, 48 (16.3%) were WB indeterminate and of those 15 (31.3%) were PCR+. Quantitative real-time PCR (qPCR) was performed to 52 HTLV-1+ samples, classified as Group 1 (G1): 25 WB+ samples from individuals with pathologies; Group 2 (G2): 18 WB+ samples from asymptomatic carriers (AC); and Group 3 (G3): 9 seroindeterminate samples from AC. Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003) was observed. Age and sex were associated with PVL in G1 and G2, respectively. Mutations in the distal and central regions of Tax Responsive Elements (TRE) 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03).

Conclusions: indeterminate WB results confirmed later as HTLV-1 positive may be associated with low PVL levels. Mutations in LTR and tax are described; their functional relevance remains to be determined.

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Related in: MedlinePlus

Individual proviral load values (PVLs). PVLs are expressed as HTLV-1 copies/100 PBMCs. (a) Samples are classified as Group 1: positive samples by Western blot (WB) from individuals with pathology that are not on treatment (n = 25), Group 2: positive samples by WB from asymptomatic carriers (AC) (n = 15), and Group 3: indeterminate samples by WB from AC (n = 4); PVL values are shown. A significant difference is observed between the three groups (p= 0.003) (GraphPad Prism V5). (b) PVLs for samples of Group 1, classified by disease: ATLL (n = 4) or HAM/TSP (n = 21) are shown, p= 0.07.
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viruses-07-02897-f002: Individual proviral load values (PVLs). PVLs are expressed as HTLV-1 copies/100 PBMCs. (a) Samples are classified as Group 1: positive samples by Western blot (WB) from individuals with pathology that are not on treatment (n = 25), Group 2: positive samples by WB from asymptomatic carriers (AC) (n = 15), and Group 3: indeterminate samples by WB from AC (n = 4); PVL values are shown. A significant difference is observed between the three groups (p= 0.003) (GraphPad Prism V5). (b) PVLs for samples of Group 1, classified by disease: ATLL (n = 4) or HAM/TSP (n = 21) are shown, p= 0.07.

Mentions: Individual PVL values are shown in Table 3. Median PVL values and standard errors were 4.78 (2.4), 2.38 (1.02), and 0.15 (0.07) HTLV-1 copies/100 PBMCs for G1, G2, and G3, respectively; a significant difference could be observed between the three groups (p = 0.003), as shown in Figure 2a. The difference was also significant (p = 0.005) when samples with seropositive WB results were analyzed as a single group [G1 + G2]. As shown in Figure 2b, no significant difference (p = 0.07) was observed when samples from acute leukemia (ATL; n = 4) were compared with HAM/TSP ones (n = 21).


Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

Cánepa C, Salido J, Ruggieri M, Fraile S, Pataccini G, Berini C, Biglione M - Viruses (2015)

Individual proviral load values (PVLs). PVLs are expressed as HTLV-1 copies/100 PBMCs. (a) Samples are classified as Group 1: positive samples by Western blot (WB) from individuals with pathology that are not on treatment (n = 25), Group 2: positive samples by WB from asymptomatic carriers (AC) (n = 15), and Group 3: indeterminate samples by WB from AC (n = 4); PVL values are shown. A significant difference is observed between the three groups (p= 0.003) (GraphPad Prism V5). (b) PVLs for samples of Group 1, classified by disease: ATLL (n = 4) or HAM/TSP (n = 21) are shown, p= 0.07.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664970&req=5

viruses-07-02897-f002: Individual proviral load values (PVLs). PVLs are expressed as HTLV-1 copies/100 PBMCs. (a) Samples are classified as Group 1: positive samples by Western blot (WB) from individuals with pathology that are not on treatment (n = 25), Group 2: positive samples by WB from asymptomatic carriers (AC) (n = 15), and Group 3: indeterminate samples by WB from AC (n = 4); PVL values are shown. A significant difference is observed between the three groups (p= 0.003) (GraphPad Prism V5). (b) PVLs for samples of Group 1, classified by disease: ATLL (n = 4) or HAM/TSP (n = 21) are shown, p= 0.07.
Mentions: Individual PVL values are shown in Table 3. Median PVL values and standard errors were 4.78 (2.4), 2.38 (1.02), and 0.15 (0.07) HTLV-1 copies/100 PBMCs for G1, G2, and G3, respectively; a significant difference could be observed between the three groups (p = 0.003), as shown in Figure 2a. The difference was also significant (p = 0.005) when samples with seropositive WB results were analyzed as a single group [G1 + G2]. As shown in Figure 2b, no significant difference (p = 0.07) was observed when samples from acute leukemia (ATL; n = 4) were compared with HAM/TSP ones (n = 21).

Bottom Line: Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003) was observed.Age and sex were associated with PVL in G1 and G2, respectively.Mutations in the distal and central regions of Tax Responsive Elements (TRE) 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03). indeterminate WB results confirmed later as HTLV-1 positive may be associated with low PVL levels.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. canepa.camila@gmail.com.

ABSTRACT

Background: indeterminate Western blot (WB) patterns are a major concern for diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) infection, even in non-endemic areas.

Objectives: (a) to define the prevalence of indeterminate WB among different populations from Argentina; (b) to evaluate if low proviral load (PVL) is associated with indeterminate WB profiles; and (c) to describe mutations in LTR and tax sequence of these cases.

Results: Among 2031 samples, 294 were reactive by screening. Of them, 48 (16.3%) were WB indeterminate and of those 15 (31.3%) were PCR+. Quantitative real-time PCR (qPCR) was performed to 52 HTLV-1+ samples, classified as Group 1 (G1): 25 WB+ samples from individuals with pathologies; Group 2 (G2): 18 WB+ samples from asymptomatic carriers (AC); and Group 3 (G3): 9 seroindeterminate samples from AC. Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003) was observed. Age and sex were associated with PVL in G1 and G2, respectively. Mutations in the distal and central regions of Tax Responsive Elements (TRE) 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03).

Conclusions: indeterminate WB results confirmed later as HTLV-1 positive may be associated with low PVL levels. Mutations in LTR and tax are described; their functional relevance remains to be determined.

Show MeSH
Related in: MedlinePlus