Sierra and Andrea working in a biosafety cabinet in the BL3

Publications

Recent and featured papers from TCF Lab.

For a complete listing of Friedrich Lab papers, please see Tom’s complete NCBI Bibliography.

Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.

Dudley et al. Nat Med. 2018

A meta-analysis of studies conducted across multiple research centers shows that Zika virus infection during pregnancy significantly increases risk of miscarriage or stillbirth, suggesting that pregnancy loss is an under-appreciated complication of Zika virus infection in humans.

PubMed link

Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics.

Aliota et al. PLoS Pathog. 2018

A collaborative study in which we constructed libraries of Zika viruses bearing randomized silent mutations (molecular barcodes) to define how viral diversity changes with time during infection.

PubMed link

Infection via mosquito bite alters Zika virus tissue tropism and replication kinetics in rhesus macaques.

Dudley et al. Nat Commun. 2017

Here we show that infected mosquitoes can deliver Zika virus to macaque monkeys. Mosquito infection delayed the time to peak virus load and was associated with dramatic changes in Zika virus genetic diversity in infected monkeys. Mosquito infection is tractable in the laboratory and may slow the pace of Zika evolution.

PubMed link

Oropharyngeal mucosal transmission of Zika virus in rhesus macaques.

Newman et al. Nat Commun. 2017

Human case reports suggest that Zika virus could, in certain circumstances, be transmitted by kissing or other contact. We used a nonhuman primate model to show that transmission via oral exposure is theoretically possible, but likely requires a high dose of virus that is not found in body fluids of most Zika-infected individuals.

PubMed link

Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans.

Dinis, Florek et al. J Virol. 2016

Using Illumina deep sequencing, we examined the genetic diversity of influenza viruses infecting individual humans. We found some mutants with the potential to escape from antibody responses, but these were always present at low frequency and there was no evidence that natural selection was acting to increase their frequency. This study suggests that beneficial influenza virus variants are not efficiently selected over the course of a single human infection.

PubMed link

Diversity of Influenza A(H5N1) Viruses in Infected Humans, Northern Vietnam, 2004-2010.

Imai et al. Emerg Infect Dis. 2018

We define genetic and phenotypic diversity of H5N1 avian influenza viruses infecting humans. Surprisingly, although we detect within-host diversity, there is little evidence for adaptation to humans during a single spillover infection.

PubMed link

An updated influenza A(H3N2) vaccine generates limited antibody responses to previously encountered antigens in children.

Florek et al. Vaccine. 2018

It has been proposed that vaccines containing antigenically novel influenza strains can also boost responses to previously circulating strains. Here we show that this “back boost” effect is weak in children, who have limited influenza exposure histories.

PubMed link

A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.

Florek et al. Plos ONE. 2017

Here we show that a nonreplicating viral vector encoding an artificial “mosaic” H5 hemagglutinin protein provides a degree of heterosubtypic protection against a pandemic H1N1 influenza virus in macaques. Antibodies raised by the vaccine do not effectively neutralize H1N1 viruses, so protection is likely to be mediated by T cells and/or non-neutralizing antibody effector mechanisms like ADCC.

PubMed link

Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus.

Moncla et al. Cell Host Microbe. 2016

This study shows that transmission bottlenecks might become more selective and less random as avian influenza viruses adapt to airborne transmission in mammals. This suggests that natural selection could drive a kind of “phase transition” in avian flu host jumping, accelerating adaptation once beneficial variants randomly arise.

This paper is the cornerstone of one of our major current projects and was a featured article in Cell Host & Microbe.

PubMed link

Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses.

Wilker, Dinis et al. Nat Commun. 2013

Here we show that natural selection on the hemagglutinin attachment protein drives genetic bottlenecks as H5N1 influenza viruses adapt to become transmissible between mammals. We further show that viral variants present frequencies as low as 6% in one host can be transmitted by respiratory droplet.

These findings established our interest in transmission bottlenecks and suggest that natural selection could effectively winnow low-frequency transmissible variants from within a viral population.

PubMed link