|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A319T |
|
Mutation Site Sentence
|
We examined the highly variable N and C-terminal region amino acid residues K305Q, I307T, H308T, R315Q, F317L, A319T, and D322R (Fig 7), 3 of which (K305Q, I307T, and H308T) have previously been identified critical targets of the V3-specific IgG responses associated with reduced MTCT risk. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
Env |
|
Standardized Encoding Gene
|
Env
|
|
Genotype/Subtype
|
HIV-1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
|
|
Immune
|
Y |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
- |
|
Location
|
America |
|
Literature Information
|
|
PMID
|
29672607
|
|
Title
|
Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma
|
|
Author
|
Kumar A,Smith CEP,Giorgi EE,Eudailey J,Martinez DR,Yusim K,Douglas AO,Stamper L,McGuire E,LaBranche CC,Montefiori DC,Fouda GG,Gao F,Permar SR
|
|
Journal
|
PLoS pathogens
|
|
Journal Info
|
2018 Apr 19;14(4):e1006944
|
|
Abstract
|
Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Also, these infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants (p = 0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could further reduce infant HIV-1 infection risk.
|
|
Sequence Data
|
MH012257-MH013187
|
|
|