Uninfected

HCMV infected

Virology in the Department of Microbiology at UAB

Virus/Host Interactions

Picornaviridae

HCV Dicistroviridae

Sunnie Thompson Richard Whitley

Herpesviridae

Quanjun Li

Translation Apoptosis

Drug Discovery

Therapeutic &

Vaccine

Development

William Britt Allan Zajac

Dengue Reoviridae

Togaviridae

Herpesviridae

(HCMV) Arenaviridae

LCMV

Assembly Immunity

Inflammation

Viral Immunology

Identification of Host Factors Involved in Viral Amplification

ILF3

Matrin‐3

hnRNPU

Nucleolin

P72

PABP1

IMP1

hnRNPL

PTB

La

hnRNPK

hnRNPG

PCBP2

hnRNPA2/B1

hnRNPC1/C2

1.

AAAAAAA

Host Factors

VPg Polyprotein

2.

170- 130-

95-

72-

55-

43-

34-

26-

1 2 3 4

Mock Polio

kDa

3.

1.  Infect cells with virus

2.  Crosslink proteins to viral

RNA in vivo 3.  Identify proteins

4.  Determine their role in

the viral life cycle

Sunnie Thompson

Spahnetal.(2001)Science291:1959‐62

HCVIRESCrPVIGRIRES

Schuleretal.(2006)Nat.Sturct.Mol.Biol.13:1092‐6

Esite

DepleKonofRPS25inhibitsHCV

replicaKonincellculture.

RPS25isnotanessenKalprotein.

RPS25isagoodtargetforanKviral

oranKcancertherapeuKcs.

FutureDirec9ons:

1.  CanHCVdevelopescapemutantsthatnolongerrequireRPS25.

2.  UseyeastgeneKcstoidenKfywhichRps25paminoacidsinteractwiththeIRESs

3.  IdenKfyinhibitorstoRPS25todevelopanKvirals

Sunnie Thompson

RPS25 is essential for translation initiation by the Dicistroviridae and hepatitis C viral IRESs Landry et al. (2009) 23: 2764

Richard Whitley

ProbethenaturalhistoryofhumanherpessimplexvirusinfecKonstodeterminevirulencefactors

EngineerHerpesSimplexVirustobeusedfortherapeuKcpurposes

–  TherapyofGlioblastomamulKforme

–  Expressforeigngenes

– UseasavectorforHIVanKgens

– DevelopaliveaZenuatedherpessimplexvaccine

Richard Whitley

Identification of Novel Antivirals against Dengue and Other Mosquito-Borne Diseases

•  Drugdiscoveryanddevelopment

– An9virals•  Denguevirus(Flaviviridae)andotherArboviruses

•  Bluetonguevirus(Reoviridae)

– An9‐malaria

•  Plasmodiumfalciparum

•  Host‐vector‐pathogeninterac9ons

– Mechanismofac9onstudiesfornovelan9virals

– An9viralefficacyevalua9oninanimalmodels

–  TheroleofapoptosisduringArbovirusinfec9on

Quanjun Li

1) Assembly of Human Cytomegalovirus

2) Immunological Control of Virus Infection of CNS

3) Inflammation and Altered Neurodevelopment

4) Vaccine development for Human Cytomegalovirus

5) Role of Virus Induced Inflammation and Allograft Loss

Bill Britt: HCMV

William Britt

William Britt

HCMV as a model

β-herpesvirus

VIRAL IMMUNOLOGY

Key Questions: Why are certain infections rapidly controlled?

Why are certain infections never controlled?

Approaches: Determining the cellular, molecular, and biochemical

properties of “protective” and “exhausted” T cell

responses

Allan Zajac

Protracted Virus slowly cleared Infection e.g. LCMV-clone 13 Infection

of Normal Adult Mice

Acute Virus rapidly cleared Infection e.g. LCMV-Armstrong

Infection of Normal Adult Mice

Lifelong Virus never cleared Infection e.g. LCMV Infection of Certain

Immunocompromised Mice

Successful versus Unsuccessful Infection Control

Allan Zajac

Structural Virology

VSV Influenza

NMR

X-Ray Crystallography

Antivirals

HIV HIV Bacteriophage 80α

HIV Bacteriophage P22

Cryo-EM

X-Ray Crystallography

Mass Spectrometry

Nano particles

Virus structure and Assembly

Ming Luo Jamil Saad Terje Dokland Peter Prevelige

Biochemical, Biophysical and Structural Biology Tools are employed to study HIV-host interactions

Jamil Saad

State-of-the-art 700 MHz NMR Instrument

Protein‐proteininterac9ons

studiedbyNMRmethods

NuclearMagne9cResonance

(NMR)

Jamil Saad

Crystal Structure Cartoon

VSV Nucleocapsid-like Particle: Structure

(Green et al., Science, 2006, 313:357-360.)

Ming Luo

The N-terminus and an extended loop near the C-

terminal domain make extensive cross-molecule

interactions, required for encapsidation of the RNA

Hemagglutinin (HA) glycoprotein trimer

Influenza virus entry

Influenza virus Attachment and Entry

Ming Luo

The 200kV FEG electron microscope at UAB

Cryo-electron microscopy of viruses

Terje Dokland

Cryo-electron microscopy allows biological structures to be

visualized in their native state, in the absence of staining, fixation

and dehydration artifacts.

HIV VLPs Staphylococcus aureus bacteriophage 80α

• 13Å 3D reconstruction of 80α

Cryo-electron microscopy of viruses

Terje Dokland

 Capsidis60nmdiameter,420proteinsubunits

 10nmholesallowsolventaccess

 Stabletohightemperature

 Caninsertpep9desthataredisplayedonoutside

 Canvarythenumberofpep9detagstotunetheavidity

 Candoinvivophagedisplaytotargettumors

 Cancarrycargoinside:

 fluorophoresandgadoliniumforimaging

 semiconductorsforenergy

 proteinsfortherapy

ProcapsidShell WiffleBall

Bio-nanotechnology using P22 Virus Capsids as a Platform for Medical and Energy Science

http://www.microbio.uab.edu/faculty/prevelige/index.html

Peter Prevelige

In vivo fluorescence imaging (FMT) of carotid arteries

RGD4C‐HFn　injectedmouse

Pre 24h 48h 48h

HFn　injectedmouse

48h 24h 48h Pre

Peter Prevelige

• CollaboratorwithModelSystem

wherethereisaneedforimproved

imaging

• facilitywithanimalmodeland

willingnesstoparKcipate

• IdenKficaKonoftargeKngtagsfor

iniKaldevelopmentstage

Collaborations

Peter Prevelige

Viral Genomics and Evolution

Poxviridae

HCV Dengue

Viral Evolution Origin of viruses

Bioinformatics Viral Evolution Viral Genomics

HIV SIV

HIV KSHV HCV

AIDS-associated lymphoma

Beatrice Hahn Elliot Lefkowitz

Epidemiology

Richard Kraslow

Viral genomics and Evolution

•  Roleofindividualgenesinvirus

replicaKon,hostinteracKon,

virulence,andpathogenesisElliot Lefkowitz

•  Analysisofgenomesequence,gene

expression,immuneinteracKon,andhost

pathwayinteracKoninformaKonuKlizing(and

developing)bioinformaKcstoolsand

techniques

•  Understandingtheprocessandconsequences

ofvirusdiversityandevoluKon

Origins of Poxvirus HT Genes

22

Nu

mb

er o

f g

enes Elliot Lefkowitz

Poxvirus:Host Co-Speciation

Elliot Lefkowitz

Immunogenetic determinants in AIDS

Richard Kraslow

•  Molecular genetics and epidemiology are applied to examine how human gene variations determine the occurrence and outcome of infectious and other diseases of immunity.

Approach:

Findings:

•  Demonstrated the strong influence of multiple combinations of polymorphic markers in the HLA region on the outcome of HIV-1 infection

Origin and Evolution of Lentiviruses

 First to describe the genetic variability

of HIV-1

 Traced the Origins of HIV-1 to Cameroon

 Discovered that recombination between highly divergent

viruses represents a major driving force of HIV and SIV

diversification

 Discovered that SIVcpz is pathogenic (AIDS-like

disease) in wild-living chimpanzees

Beatrice Hahn

Additional Faculty

•  PaulGoepfert,M.D. Virology;vaccines

•  JohnKappes,Ph.D. HIV;molecularvirologyandpathogenesis

•  CaseyMorrow,Ph.D. Viralmorphogenesisandreplica9ongene

therapyandvaccines

•  GeorgeShaw,M.D. Humanretroviruses;molecularvirologyan

pathogenesis

•  WayneSullender,M.D. Respiratorysyncy9alvirus;an9genic

diversity

•  MarkPritchard,Ph.D. HerpesandOrthopoxAn9virals