title: Mycobacterium smegmatis - Comparison of amtR deletion strain YL1 under nitrogen surplus and starvation

first: Weber

last: Simone

address: Ulmenweg 18

summary:
In this approach, total transcript of a Mycobacterium smegmatis amtR deletion strain was compared under nitrogen surplus and starvation. This is a control experiment to the comparison of wild type and amtR deletion strain, resulting nitrogen-related genes which are not AmtR-controlled.
Two biological replicates were analyzed.

first: Stephen

last: Reid

first: Sophia


title: Nef-mediated downmodulation of CD3 dampens immune activation and is critical for maintenance of high virus loads in SIV-infected macaques

status: Public on Mar 09 2020

city: Atlanta

first: Gregory

middle: K

last: Tharp

state: GA

address: 954 Gatewood Dr

department: Developmental and Cognitive Neuroscience

country: USA

institute: Yerkes National Primate Research Center

type: Expression profiling by high throughput sequencing

summary: The inability of Nef to downmodulate the T cell receptor CD3 distinguishes HIV-1 from most other primate lentiviruses and may contribute to its high virulence. However, the role of this Nef function in viral immune evasion and pathogenicity remained speculative. Here, we selectively disrupted this Nef activity in SIVmac239 and analyzed the consequences for the virological, immunological and clinical outcome of infection in rhesus macaques. The inability to downmodulate CD3 did not affect viral replication during acute infection but was associated with increased immune activation and antiviral gene expression. Thus, Nef-mediated downmodulation of CD3 dampens the inflammatory response to SIV infection and is critical for viral immune evasion.

overall_design:
Twelve young adult rhesus macaques were distributed to two groups with six monkeys each. Animals in the first group (n=6) were inoculated intravenously with infectious doses of CD3ko-Nef SIVmac239 (CD3ko), SIVmac239 containing 2 point mutations in Nef. The animals of the other group (n=6) received SIVmac239 wild type (wt) at the same dose and by the same route as for the mutant virus.
Blood samples (PBMC) were collected and peripheral lymph nodes (LN) were surgically removed before and post-infection.
The samples were collected in two sets of experiments, A and B. Set A consists of PBMC and LN samples from wt (n=3) and CD3ko (n=3) infected animals at 2 weeks post-infection. For Set A, PBMC samples were also collected from uninfected control animals (n=10). Set B consists of PBMC and LN samples from wt (n=3) and CD3ko (n=3) infected animals at both pre- and post-infection time-points.

first: Simone

last: Joas

first: Ulrike

last: Sauermann

first: Berit

last: Neumann

first: Antonina

last: Klippert

first: Nicole

last: Stolte-Leeb

first: Anke

last: Heigele

first: Jan

last: Schmökel

first: Sydney

middle: A

last: Nelson

first: Prachi

middle: M

last: Gupta

first: Steven

last: Bosinger

first: Laura

last: Parodi

first: Luis

last: Giavedoni

first: Guido

last: Silvestri

first: Daniel

last: Sauter

first: Christiane

last: Stahl-Hennig

first: Frank

last: Kirchhoff