Step 1 · Microbiology

DNA & RNA Viruses

Name: DNA & RNA Viruses
Creator: Veli Bakalov, MD

Family rules and buzzwords from herpes to influenza

Microbiology·Virology·4 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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DNA viruses are dsDNA except parvovirus (ssDNA), replicate in the nucleus except poxvirus (cytoplasm, own DNA-dependent RNA polymerase), and are enveloped except PAPP (papilloma, adeno, parvo, polyoma).
Herpes latency: HSV-1 trigeminal ganglion, HSV-2 sacral ganglia, VZV dorsal root/trigeminal ganglia, EBV B cells; HHV-6 roseola, HHV-8 Kaposi sarcoma.
EBV enters B cells via CD21 and causes heterophile-positive mono with atypical CD8 T cells (plus Burkitt, nasopharyngeal carcinoma); CMV causes heterophile-negative mono, owl-eye inclusions, congenital infection, AIDS retinitis.
HPV E6 degrades p53 and E7 inhibits Rb; JC virus → PML in AIDS; BK virus → transplant nephropathy; adenovirus → pharyngitis, conjunctivitis, recruit pneumonia.
Parvovirus B19 (binds P antigen on erythroid precursors): slapped-cheek fifth disease, aplastic crisis in sickle cell, hydrops fetalis, adult arthralgias.
RNA viruses are ssRNA except reovirus, replicate in the cytoplasm except influenza and retroviruses; segmented = BOAR (Bunya, Orthomyxo, Arena, Reo).
Negative-sense viruses (Arena, Bunya, Paramyxo, Orthomyxo, Filo, Rhabdo) must package RNA-dependent RNA polymerase; positive-sense genomes are translated directly.
Rabies: bullet-shaped, binds nicotinic AChR, retrograde axonal transport, Negri bodies in hippocampal/Purkinje neurons; postexposure wound care + immunoglobulin + vaccine.
Paramyxovirus F protein makes giant cells (RSV bronchiolitis, croup, measles with Koplik spots, mumps); influenza drift = point mutations (epidemics), shift = segment reassortment (pandemics).

DNA viruses: the family rules

Three rules with one exception each. Almost every DNA virus question can be answered from these:

Strandedness: all are double-stranded except Parvovirus (single-stranded, and the smallest).
Replication site: all replicate in the nucleus except Poxvirus (cytoplasm).
Envelope: all are enveloped except the naked PAPP viruses: Papilloma, Adeno, Parvo, Polyoma.

Viruses that bring a polymerase. Poxvirus and hepadnavirus (HBV) carry their own polymerase. Poxvirus packages a DNA-dependent RNA polymerase because it replicates entirely in the cytoplasm, away from the host's nuclear transcription machinery.

Herpesviruses

Shared biology. Herpesviruses are enveloped dsDNA viruses that establish lifelong latency and reactivate when immunity wanes. HSV and VZV lesions show multinucleated giant cells on Tzanck smear and Cowdry A intranuclear inclusions.

The eight human herpesviruses

Virus	Key diseases	Latency / clue
HSV-1	Oral lesions, keratitis, temporal-lobe encephalitis	Trigeminal ganglion
HSV-2	Genital herpes	Sacral ganglia
VZV (HHV-3)	Varicella, zoster	Dorsal root and trigeminal ganglia
EBV (HHV-4)	Mononucleosis, Burkitt lymphoma, nasopharyngeal carcinoma	B cells (enters via CD21)
CMV (HHV-5)	Heterophile-negative mono, congenital infection, retinitis in AIDS	Owl-eye inclusions
HHV-6 and HHV-7	Roseola (days of high fever, then rash)	HHV-6 is the usual cause
HHV-8	Kaposi sarcoma	AIDS and transplant patients

EBV vs CMV mononucleosis. Mononucleosis presents with fever, pharyngitis, posterior cervical lymphadenopathy, and splenomegaly. EBV infects B cells through CD21; the atypical lymphocytes on smear are reactive CD8 T cells. EBV mono is heterophile-positive (Monospot), while CMV causes a heterophile-negative mono, so a mono picture with a negative Monospot points to CMV. Splenomegaly in EBV mono carries a risk of rupture, so contact sports are avoided. CMV is also the most common congenital viral infection and causes retinitis in advanced AIDS.

Other DNA viruses

HPV (naked). E6 degrades p53 and E7 inhibits Rb, releasing the cell cycle from control. High-risk types (16, 18) drive cervical, anal, and oropharyngeal cancer; low-risk types (6, 11) cause warts.

Adenovirus (naked). Febrile pharyngitis, "pink eye" conjunctivitis, and pneumonia in military recruits; it also causes hemorrhagic cystitis.

Polyomaviruses. JC virus causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease, in AIDS; BK virus causes nephropathy in transplant recipients.

Parvovirus B19 (ssDNA, naked, smallest). It binds the P antigen (globoside) on erythroid precursors and halts red-cell production. Presentations:

Children: erythema infectiosum (fifth disease), a slapped-cheek rash.
Sickle cell disease: aplastic crisis with near-absent reticulocytes.
Pregnancy: fetal anemia and hydrops fetalis.
Adults: pure arthralgias.

Poxviruses. The largest viruses: dsDNA, enveloped, and unique in replicating in the cytoplasm using their own DNA-dependent RNA polymerase. Examples are smallpox (variola) and molluscum contagiosum (umbilicated papules).

RNA viruses: the family rules

Strandedness: single-stranded except Reovirus (double-stranded).
Replication site: cytoplasm except Orthomyxovirus (influenza) and Retroviruses (nucleus).
Segmented: BOAR, meaning Bunya, Orthomyxo, Arena, Reo. Segments allow reassortment.
Naked: Calici, Picorna, Reo, Hepe.

Positive- vs negative-sense RNA viruses

Feature	Positive-sense	Negative-sense
Families	Retro, Toga, Flavi, Corona, Hepe, Calici, Picorna	Arena, Bunya, Paramyxo, Orthomyxo, Filo, Rhabdo
Genome	Acts directly as mRNA and is translated immediately	Complementary to mRNA; must be transcribed first
Virion enzyme	None needed to start (retroviruses carry reverse transcriptase)	Must package RNA-dependent RNA polymerase
Purified genome infectious?	Yes (except retroviruses)	No

Negative-sense mnemonic: Always Bring Polymerase Or Fail Replication.

Retroviruses are the exception among positive-sense viruses: their genome is reverse-transcribed into DNA and integrated before any translation.

High-yield RNA families

Picornaviruses (naked, positive-sense). The genome is translated as one polyprotein that viral proteases cleave. PERCH: Poliovirus, Echovirus, Rhinovirus, Coxsackievirus, HAV. Coxsackie causes aseptic meningitis, herpangina, hand-foot-mouth disease, and myocarditis. Rhinovirus causes the common cold and is acid-labile, so it cannot survive the stomach.

Flaviviruses (enveloped, positive-sense). HCV plus the arthropod-borne yellow fever, dengue, West Nile, Zika, and St. Louis encephalitis viruses. Dengue causes "breakbone fever"; a second infection with a different serotype can cause hemorrhagic fever through antibody-dependent enhancement.

Rhabdovirus: rabies. A bullet-shaped, negative-sense virus with a long incubation period, acquired from bat, dog, raccoon, or skunk bites.

Animal biteVirus replicates locally in muscle
Binds nicotinic ACh receptorsEnters nerve terminals
Retrograde axonal transportSlow climb to the CNS explains the long incubation
EncephalitisNegri bodies in hippocampal and Purkinje neurons; agitation, hypersalivation, hydrophobia, coma

Rabies pathogenesis

Negri bodies are eosinophilic cytoplasmic inclusions. Postexposure prophylaxis (wound cleaning plus rabies immunoglobulin plus vaccine) works because of the long incubation.

Paramyxoviruses (negative-sense). The F (fusion) protein fuses infected cells into multinucleated giant cells.

RSV: bronchiolitis in infants; anti-F monoclonal antibodies (long-acting nirsevimab now, palivizumab formerly) or maternal RSV vaccination protect infants.
Parainfluenza: croup, with a seal-like barking cough and steeple sign.
Measles: the 3 Cs (cough, coryza, conjunctivitis) plus Koplik spots; subacute sclerosing panencephalitis (SSPE) years later.
Mumps: parotitis, orchitis, and aseptic meningitis.

Orthomyxovirus: influenza. A segmented, negative-sense virus. Hemagglutinin mediates attachment and neuraminidase releases new virions; neuraminidase inhibitors (oseltamivir, zanamivir) block that release. Secondary bacterial pneumonia, notably S. aureus, is a classic complication.

Influenza drift vs shift

Feature	Antigenic drift	Antigenic shift
Mechanism	Point mutations in HA/NA genes	Reassortment of whole segments between strains co-infecting a cell
Size of change	Small	Large: novel HA/NA
Consequence	Epidemics; yearly vaccine updates	Pandemics