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Published on: September 1, 2015
A dual role for Mannan-binding lectin-associated serine protease 2 (MASP-2) in HIV infection
Angelica Beate Winter Boldt1, Márcia Holsbach Beltrame2, Sandra Jeremias Catarino2
1Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil; Laboratório de Genética Molecular Humana, Universidade Federal do Paraná, Curitiba, Brazil.
Background:
Mannan-binding lectin (MBL) - associated serine protease 2 (MASP-2) co-activates the lectin pathway of complement in response to several viral infections. The quality of this response partly depends on MASP2 gene polymorphisms, which modulate MASP-2 function and serum levels. In this study we investigated a possible role of MASP2 polymorphisms, MASP-2 serum levels and MBL-mediated complement activation in the susceptibility to HIV/AIDS and HBV/HCV coinfection.
Methods:
A total of 178 HIV patients, 89 (50%) coinfected with HBV/HCV, 51.7% female, average age 40 (12-73) years, and 385 controls were evaluated. MASP-2 levels and MBL-driven complement activation were evaluated by enzyme-linked immunosorbent assay and 11 MASP2 polymorphisms from the promoter to the last exon were haplotyped using multiplex sequence-specific PCR.
Results:
Genotype distribution was in Hardy-Weinberg equilibrium and differed between HIV+ patients and controls (P=0.030), irrespective of HBV or HCV coinfection. The p.126L variant, which was associated with MASP-2 levels <200ng/mL (OR=5.0 [95%CI=1.3-19.2] P=0.019), increased the susceptibility to HIV infection (OR=5.67 [95%CI=1.75-18.33], P=0.004) and to HIV+HBV+ status (OR=6.44 [95%CI=1.69-24.53, P=0.006). A similar association occurred with the ancient haplotype harboring this variant, AGCDV (OR=2.35 [95%CI=1.31-4.23], P=0.004). On the other hand, p.126L in addition to other variants associated with low MASP-2 levels-p.120G, p.377A and p.439H, presented a protective effect against AIDS (OR=0.25 [95%CI=0.08-0.80], P=0.020), independently of age, sex, hepatic function and viral load. MASP-2 serum levels were lower in HIV+ and HIV+HBV+ patients than in controls (P=0.0004). Among patients, MASP-2 levels were higher in patients with opportunistic diseases (P=0.001) and AIDS (P=0.004). MASP-2 levels correlated positively with MBL/MASP2-mediated C4 deposition (r=0.29, P=0.0002) and negatively with CD4+ cell counts (r=-0.21, P=0.018), being related to decreased CD4+ cell counts (OR=5.8 [95%CI=1.23-27.5, P=0.026).
Conclusions:
Genetically determined MASP-2 levels seem to have a two-edge effect in HIV and probably HCV/HBV coinfection, whereas low levels increase the susceptibility to infection, but on the other side protects against AIDS.
Insights
Mannan-binding lectin-associated serine protease 2 (MASP-2) gene variants influence susceptibility to HIV infection and AIDS progression. Low MASP-2 levels increase HIV susceptibility but offer protection against developing AIDS.
Area of Science:
- Immunogenetics
- Complement System
- Viral Pathogenesis
Background:
- Mannan-binding lectin-associated serine protease 2 (MASP-2) activates the complement lectin pathway, crucial in viral infections.
- MASP2 gene polymorphisms affect MASP-2 function and serum levels, potentially influencing disease outcomes.
- Understanding MASP-2's role is vital in managing HIV/AIDS and HBV/HCV coinfections.
Purpose of the Study:
- To investigate the association between MASP2 polymorphisms, MASP-2 serum levels, and MBL-mediated complement activation.
- To determine the role of these factors in susceptibility to HIV/AIDS and HBV/HCV coinfection.
Main Methods:
- Evaluated 178 HIV patients (89 coinfected with HBV/HCV) and 385 controls.
- Measured MASP-2 serum levels and MBL-driven complement activation using ELISA.
- Haplotyped 11 MASP2 polymorphisms using multiplex sequence-specific PCR.
Main Results:
- MASP2 genotype distribution differed between HIV+ patients and controls (P=0.030).
- The p.126L variant, associated with low MASP-2 levels, increased susceptibility to HIV infection and HIV+HBV+ status.
- Low MASP-2 levels were linked to protection against AIDS progression but correlated with lower CD4+ cell counts.
Conclusions:
- Genetically determined MASP-2 levels exhibit a dual effect in HIV and viral coinfections.
- Low MASP-2 levels enhance susceptibility to initial infection.
- Conversely, low MASP-2 levels appear protective against the development of AIDS.
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