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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

Western blot patterns of indeterminate cases confirmed HTLV-1 positive by n-PCR. Seroreactivity pattern using the MPD HTLV Blot 2.4 kit, which contains a recombinant GD21 (common for HTLV-1 and HTLV-2) and two synthetic peptides (rpg46-I and rpg46-II), specific either for HTLV-1 or HTLV-2. “HTLV-1”: HTLV-1 positive control. “C-“: negative control. 44–52: banding profile for each of the nine seroindeterminate cases analyzed.
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viruses-07-02897-f001: Western blot patterns of indeterminate cases confirmed HTLV-1 positive by n-PCR. Seroreactivity pattern using the MPD HTLV Blot 2.4 kit, which contains a recombinant GD21 (common for HTLV-1 and HTLV-2) and two synthetic peptides (rpg46-I and rpg46-II), specific either for HTLV-1 or HTLV-2. “HTLV-1”: HTLV-1 positive control. “C-“: negative control. 44–52: banding profile for each of the nine seroindeterminate cases analyzed.

Mentions: The following experiments were performed in nine out of 13 seroindeterminate confirmed HTLV-1 positive cases found among the four studied populations, as samples from the other four were scarce. Figure 1 shows the banding pattern in each case.


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)

Western blot patterns of indeterminate cases confirmed HTLV-1 positive by n-PCR. Seroreactivity pattern using the MPD HTLV Blot 2.4 kit, which contains a recombinant GD21 (common for HTLV-1 and HTLV-2) and two synthetic peptides (rpg46-I and rpg46-II), specific either for HTLV-1 or HTLV-2. “HTLV-1”: HTLV-1 positive control. “C-“: negative control. 44–52: banding profile for each of the nine seroindeterminate cases analyzed.
© Copyright Policy
Related In: Results  -  Collection

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

viruses-07-02897-f001: Western blot patterns of indeterminate cases confirmed HTLV-1 positive by n-PCR. Seroreactivity pattern using the MPD HTLV Blot 2.4 kit, which contains a recombinant GD21 (common for HTLV-1 and HTLV-2) and two synthetic peptides (rpg46-I and rpg46-II), specific either for HTLV-1 or HTLV-2. “HTLV-1”: HTLV-1 positive control. “C-“: negative control. 44–52: banding profile for each of the nine seroindeterminate cases analyzed.
Mentions: The following experiments were performed in nine out of 13 seroindeterminate confirmed HTLV-1 positive cases found among the four studied populations, as samples from the other four were scarce. Figure 1 shows the banding pattern in each case.

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