scholarly journals A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats

2021 ◽  
Author(s):  
Shelby Winans ◽  
Stephen P. Goff
Keyword(s):  
Viral Replication ◽  
Point Mutation ◽  
Integration Site ◽  
Single Point ◽  
Host Factors ◽  
Latent Reservoir ◽  
Single Point Mutation ◽  
Site Preference ◽  
Chromosomal Dna ◽  
Hiv 1

AbstractRetroviruses utilize the viral integrase (IN) protein to integrate a DNA copy of their genome into the host chromosomal DNA. HIV-1 integration sites are highly biased towards actively transcribed genes, likely mediated by binding of the IN protein to specific host factors, particularly LEDGF, located at these gene regions. We here report a dramatic redirection of integration site distribution induced by a single point mutation in HIV-1 IN. Viruses carrying the K258R IN mutation exhibit more than a 25-fold increase in integrations into centromeric alpha satellite repeat sequences, as assessed by both deep sequencing and qPCR assays. Immunoprecipitation studies identified host factors that uniquely bind to the mutant IN protein and thus may account for the novel bias for integration into centromeres. Centromeric integration events are known to be enriched in the latent reservoir of infected memory T cells, as well as in patients who control viral replication without intervention (so-called elite controllers). The K258R point mutation in HIV-1 IN reported in this study has also been found in databases of latent proviruses found in patients. The altered integration site preference induced by this mutation has uncovered a hidden feature of the establishment of viral latency and control of viral replication.

scholarly journals A Single Point Mutation in the Rhinovirus 2B Protein Reduces the Requirement for Phosphatidylinositol 4-Kinase Class III Beta in Viral Replication

2018 ◽  
Vol 92 (23) ◽  
Author(s):  
Pascal S. Roulin ◽  
Luca P. Murer ◽  
Urs F. Greber
Keyword(s):  
Viral Replication ◽  
Point Mutation ◽  
Single Point ◽  
Host Factors ◽  
Wild Type Virus ◽  
Single Point Mutation ◽  
Class Iii ◽  
Wild Type ◽  
2B Protein ◽  
Phosphatidylinositol 4

ABSTRACTRhinoviruses (RVs) replicate on cytoplasmic membranes derived from the Golgi apparatus. They encode membrane-targeted proteins 2B, 2C, and 3A, which control trafficking and lipid composition of the replication membrane. The virus recruits host factors for replication, such as phosphatidylinositol 4 (PI4)-kinase 3beta (PI4K3b), which boosts PI4-phosphate (PI4P) levels and drives lipid countercurrent exchange of PI4P against cholesterol at endoplasmic reticulum-Golgi membrane contact sites through the lipid shuttling protein oxysterol binding protein 1 (OSBP1). We identified a PI4K3b inhibitor-resistant RV-A16 variant with a single point mutation in the conserved 2B protein near the cytosolic carboxy terminus, isoleucine 92 to threonine (termed 2B[I92T]). The mutation did not confer resistance to cholesterol-sequestering compounds or OSBP1 inhibition, suggesting invariant dependency on the PI4P/cholesterol lipid countercurrents. In the presence of PI4K3b inhibitor, Golgi reorganization and PI4P lipid induction occurred in RV-A16 2B[I92] but not in wild-type infection. The knockout of PI4K3b abolished the replication of both the 2B[I92T] mutant and the wild type. Doxycycline-inducible expression of PI4K3b in PI4K3b knockout cells efficiently rescued the 2B[I92T] mutant and, less effectively, wild-type virus infection. Ectopic expression of 2B[I92T] or 2B was less efficient than that of 3A in recruiting PI4K3b to perinuclear membranes, suggesting a supportive rather than decisive role of 2B in recruiting PI4K3b. The data suggest that 2B tunes the recruitment of PI4K3b to the replication membrane and allows the virus to adapt to cells with low levels of PI4K3b while still maintaining the PI4P/cholesterol countercurrent for establishing Golgi-derived RV replication membranes.IMPORTANCEHuman rhinoviruses (RVs) are the major cause of the common cold worldwide. They cause asthmatic exacerbations and chronic obstructive pulmonary disease. Despite recent advances, the development of antivirals and vaccines has proven difficult due to the high number and variability of RV types. The identification of critical host factors and their interactions with viral proteins and membrane lipids for the establishment of viral replication is a basis for drug development strategies. Our findings here shed new light on the interactions between nonstructural viral membrane proteins and class III phosphatidylinositol 4 kinases from the host and highlight the importance of phosphatidylinositol 4 phosphate for RV replication.

scholarly journals Impaired Infectivity of HIV-1 after a Single Point Mutation in the POL Gene to Escape the Effect of a Protease Inhibitor in Vitro

Virology ◽  
1995 ◽  
Vol 210 (1) ◽  
pp. 212-216 ◽  
Author(s):  
Marcelo J. Kuroda ◽  
Mohamed A. El-Farrash ◽  
Suranjana Choudhury ◽  
Shinji Harada
Keyword(s):  
Protease Inhibitor ◽  
Point Mutation ◽  
Single Point ◽  
Single Point Mutation ◽  
Hiv 1

A single point mutation in HIV-1 V3 loop alters the immunogenic properties of rgp120

2000 ◽  
Vol 145 (10) ◽  
pp. 2087-2103 ◽  
Author(s):  
S.-K. Lee ◽  
G. A. Pestano ◽  
J. Riley ◽  
A. S. Hasan ◽  
M. Pezzano ◽  
...  
Keyword(s):  
Point Mutation ◽  
Single Point ◽  
Single Point Mutation ◽  
V3 Loop ◽  
Immunogenic Properties ◽  
Hiv 1

scholarly journals A single point mutation converts a proton-pumping rhodopsin into a red-shifted, turn-on fluorescent sensor for chloride

2021 ◽  
Author(s):  
Jasmine N. Tutol ◽  
Jessica Lee ◽  
Hsichuan Chi ◽  
Farah N. Faizuddin ◽  
Sameera S. Abeyrathna ◽  
...  
Keyword(s):  
Point Mutation ◽  
Fluorescent Sensor ◽  
Single Point ◽  
Proton Pumping ◽  
Single Point Mutation ◽  
Turn On ◽  
Gloeobacter Violaceus

By utilizing laboratory-guided evolution, we have converted the fluorescent proton-pumping rhodopsin GR from Gloeobacter violaceus into GR1, a red-shifted, turn-on fluorescent sensor for chloride.

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