A host Ca2+/Mn2+ ion pump is a factor in the emergence of viral RNA recombinants

Hannah M Jaag1, Judit Pogany, Peter D Nagy

  • 1Department of Plant Pathology, University of Kentucky, Plant Science Building, Lexington, KY 40546, USA.

Cell Host & Microbe
|February 2, 2010
PubMed

Insights

Host protein Pmr1p influences viral RNA recombination and replication. Its role in regulating manganese (Mn2+) levels is key to controlling viral evolution and the emergence of new strains.

Area of Science:

  • Virology
  • Molecular Biology
  • Host-Pathogen Interactions

Background:

  • RNA viruses rapidly evolve through mutation and recombination.
  • Emergence of drug-resistant or highly virulent viral strains is a significant public health concern.
  • Host factors play a crucial role in modulating viral evolution.

Purpose of the Study:

  • To investigate the role of host Pmr1p, a Golgi ion pump, in viral RNA recombination and replication.
  • To determine the specific contribution of Pmr1p's ion transport function to viral RNA recombination frequency.

Main Methods:

  • Utilized yeast as a model host for Tomato bushy stunt virus (TBSV) RNA recombination studies.
  • Employed separation-of-function mutants of Pmr1p to dissect its functional domains.
  • Established a cell-free TBSV replication system to assess the impact of manganese (Mn2+) concentration.
  • Investigated the effects of Ca2+/Mn2+ exporter knockdown in plants on virus replication and recombination.

Main Results:

  • Inactivation of the host gene PMR1 resulted in a ~160-fold increase in TBSV RNA recombination in yeast.
  • Pmr1p's ability to regulate cytosolic Mn2+ concentration was identified as critical for viral RNA recombination.
  • Elevated Mn2+ levels in a cell-free system significantly increased TBSV recombination frequency.
  • Knockdown of Ca2+/Mn2+ exporters in plants enhanced both TBSV replication and RNA recombination.

Conclusions:

  • The conserved host protein Pmr1p significantly impacts viral RNA recombination and replication efficiency.
  • Cytosolic manganese (Mn2+) concentration, regulated by Pmr1p, is a key determinant of viral RNA recombination.
  • Host ion homeostasis mechanisms represent potential targets for controlling RNA virus adaptive evolution.

Related Concept Videos

Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
Intracellular Movement of Viruses and Bacteria01:10

Intracellular Movement of Viruses and Bacteria

Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a virus that...
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...