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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Functional properties of the HIV-1 subtype C envelope glycoprotein associated with mother-to-child transmission
Hong Zhang1, Marzena Rola, John T West
1Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68583-0900, USA.
Insights
Newly transmitted HIV-1 variants show distinct envelope glycoprotein properties, often evading maternal plasma neutralization but remaining susceptible to broader antibody responses. This informs strategies against perinatal HIV-1 transmission.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Perinatal transmission of Human Immunodeficiency Virus type 1 (HIV-1) remains a significant global health challenge.
- Understanding the viral characteristics that facilitate mother-to-child transmission is crucial for developing effective prevention strategies.
- Previous research indicated that newly transmitted HIV-1 strains possess enhanced growth fitness due to their envelope glycoproteins.
Purpose of the Study:
- To characterize the viral envelope glycoproteins of HIV-1 from mother-infant transmission pairs.
- To determine if specific envelope functions correlate with the efficiency of perinatal HIV-1 subtype C transmission.
- To investigate the neutralization susceptibility of newly transmitted viruses against maternal and heterologous plasma.
Main Methods:
- Analysis of viral envelope glycoproteins from six mother-infant HIV-1 transmission pairs.
- Assessment of viral susceptibility to neutralization by autologous maternal plasma and pooled heterologous plasma.
- Evaluation of neutralization resistance to specific antibodies, including IgG1 b12.
- Examination of Env processing and incorporation efficiency as potential predictors of transmissibility.
Main Results:
- Newly transmitted HIV-1 viruses exhibited reduced susceptibility to neutralization by their corresponding maternal plasma compared to maternal viruses.
- These transmitted variants were generally sensitive to neutralization by pooled heterologous plasma.
- Resistance to IgG1 b12 neutralization was observed in most newly transmitted variants.
- Neither Env processing efficiency nor incorporation efficiency correlated with viral transmissibility.
Conclusions:
- HIV-1 envelope glycoproteins play a key role in perinatal transmission, with newly transmitted strains possessing distinct neutralization resistance profiles.
- The findings suggest that while transmitted viruses can evade maternal immune responses, they may remain vulnerable to broader antibody neutralization.
- These insights are valuable for designing interventions and therapeutic strategies aimed at preventing mother-to-child HIV-1 transmission.
Abstract:
Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the newly transmitted variants were sensitive to neutralization by pooled heterologous plasma but in general were resistant to IgG1 b12. Neither Env processing nor incorporation efficiency was predictive of viral transmissibility. These findings provide further insight into the characteristics of perinatally transmissible HIV-1 and may have implications for intervention approaches.
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