14. Which one of the following enzymes is required to ensure the replication of a negative-sense or negative-strand RNA virus?

(A) DNA-dependent RNA polymerase

(B) DNA polymerase

(D) RNA-dependent RNA polymerase

RNA-Dependent RNA Polymerase in Negative-Sense RNA Viruses

Introduction

Viruses are obligate intracellular parasites that depend on host cells for replication. However, unlike cellular organisms, many viruses carry unique enzymes that are not naturally present in host cells. One of the most important of these enzymes is RNA-dependent RNA polymerase (RdRp), which is indispensable for the replication of RNA viruses. This enzyme synthesizes RNA using an RNA template, allowing RNA viruses to produce messenger RNA (mRNA) and replicate their genomes.

Negative-sense (negative-strand) RNA viruses possess genomes that are complementary to messenger RNA. Because host ribosomes cannot directly translate negative-sense RNA into proteins, these viruses must first convert their genome into positive-sense RNA. This conversion requires RNA-dependent RNA polymerase, an enzyme that is absent in normal eukaryotic cells. Consequently, all negative-sense RNA viruses carry this enzyme within the viral particle itself.

Correct Answer

Correct Option: (D) RNA-dependent RNA polymerase

Detailed Explanation

Negative-sense RNA viruses possess a genome that cannot function directly as messenger RNA. Instead, the viral RNA is complementary to the coding sequence required for protein synthesis. Therefore, immediately after entering the host cell, the virus must synthesize a complementary positive-sense RNA molecule that serves as mRNA for translation.

This process is carried out by RNA-dependent RNA polymerase (RdRp), which synthesizes RNA from an RNA template. Since animal cells do not possess RNA-dependent RNA polymerase, negative-sense RNA viruses package this enzyme within the virion before infecting a host cell. Once inside the cytoplasm (or nucleus in the case of influenza virus), RdRp transcribes the negative-sense RNA genome into positive-sense mRNA. The newly synthesized mRNA is translated by host ribosomes to produce viral proteins, including additional copies of RNA-dependent RNA polymerase required for genome replication.

Without RNA-dependent RNA polymerase, negative-sense RNA viruses would be unable to initiate protein synthesis or replicate their genomes, making this enzyme absolutely essential for their life cycle.

Explanation of Each Option

Option (A): DNA-Dependent RNA Polymerase

This option is incorrect. DNA-dependent RNA polymerase transcribes RNA from a DNA template and is used by cells and DNA viruses. It cannot synthesize RNA from an RNA template.

Option (B): DNA Polymerase

This option is incorrect. DNA polymerase synthesizes DNA using a DNA template and functions during DNA replication. It has no role in the replication of negative-sense RNA viruses.

Option (C): RNA-Dependent DNA Polymerase

This option is incorrect. RNA-dependent DNA polymerase, also known as reverse transcriptase, converts RNA into DNA. It is characteristic of retroviruses such as HIV but is not used by negative-sense RNA viruses.

Option (D): RNA-Dependent RNA Polymerase

This option is correct. RNA-dependent RNA polymerase synthesizes positive-sense RNA from a negative-sense RNA template and also replicates the viral RNA genome.

Why Option (D) is Correct

Negative-sense RNA viruses cannot be translated directly because their genome is complementary to mRNA. They require RNA-dependent RNA polymerase to synthesize positive-sense RNA that can be translated into viral proteins. This enzyme also generates new genomic RNA molecules during viral replication.

Why the Other Options are Incorrect

Why Option (A) is Incorrect

DNA-dependent RNA polymerase uses DNA templates rather than RNA templates and therefore cannot replicate RNA viruses.

Why Option (B) is Incorrect

DNA polymerase participates in DNA replication and is unrelated to the replication of RNA virus genomes.

Why Option (C) is Incorrect

Reverse transcriptase is specific to retroviruses and synthesizes DNA from RNA. Negative-sense RNA viruses do not form a DNA intermediate during replication.

Comparison of All Options

Option	Enzyme	Function	Correct or Incorrect
A	DNA-dependent RNA polymerase	RNA synthesis from DNA	Incorrect
B	DNA polymerase	DNA replication	Incorrect
C	RNA-dependent DNA polymerase	Reverse transcription	Incorrect
D	RNA-dependent RNA polymerase	RNA synthesis from RNA	Correct

Baltimore Classification and Viral Polymerases

Virus Type	Genome	Required Polymerase
dsDNA Viruses	Double-stranded DNA	DNA-dependent RNA polymerase
ssDNA Viruses	Single-stranded DNA	DNA polymerase and DNA-dependent RNA polymerase
Positive-Sense RNA Viruses	+ssRNA	Encode RNA-dependent RNA polymerase after infection
Negative-Sense RNA Viruses	−ssRNA	Carry RNA-dependent RNA polymerase in the virion
Retroviruses	+ssRNA	RNA-dependent DNA polymerase (Reverse Transcriptase)

Examples of Negative-Sense RNA Viruses

Virus	Family
Influenza Virus	Orthomyxoviridae
Rabies Virus	Rhabdoviridae
Ebola Virus	Filoviridae
Measles Virus	Paramyxoviridae
Mumps Virus	Paramyxoviridae
Respiratory Syncytial Virus (RSV)	Pneumoviridae

Comparison of Viral Polymerases

Polymerase	Template	Product	Found In
DNA Polymerase	DNA	DNA	Cells and DNA viruses
DNA-dependent RNA Polymerase	DNA	RNA	Cells and DNA viruses
RNA-dependent RNA Polymerase	RNA	RNA	RNA viruses
RNA-dependent DNA Polymerase	RNA	DNA	Retroviruses

Biological Significance

RNA-dependent RNA polymerase is one of the most important enzymes in virology because it enables RNA viruses to replicate independently of host DNA-dependent polymerases. Since mammalian cells lack this enzyme, it has become an attractive target for antiviral drug development. Several antiviral drugs used against influenza virus, hepatitis C virus, and SARS-CoV-2 target viral RNA-dependent RNA polymerase, highlighting its central role in viral replication and disease control.

Final Answer