180 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

Typhoid and typhus

Typhoid fever Caused by bacterium Salmonella typhi.
Typhus Caused by bacteria Rickettsia prowazekii (epidemic), Rickettsia typhi (endemic), and Rickettsia
tsutsugamushi (scrub typhus).

MICROBIOLOGY—VIROLOGY

Viral structure—general Naked icosahedral Enveloped icosahedral Enveloped helical

features Surface
Surface protein
protein
Nucleocapsid Matrix or
Lipid
core protein
bilayer
Nucleic acid Capsid Lipid bilayer
Nucleic Nucleid acid and
acid nucleocapsid
protein

Viral genetics
Recombination Exchange of genes between 2 chromosomes by crossing over within regions of significant base
sequence homology.
Reassortment When viruses with segmented genomes (e.g., influenza virus) exchange segments. High-frequency
recombination. Cause of worldwide influenza pandemics.
Complementation When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein. The
nonmutated virus “complements” the mutated one by making a functional protein that serves
both viruses.
Phenotypic mixing Occurs with simultaneous infection of a cell with 2 viruses. Genome of virus A can be partially
or completely coated (forming pseudovirion) with the surface proteins of virus B. Type B protein
coat determines the infectivity of the phenotypically mixed virus. However, the progeny from this
infection have a type A coat that is encoded by its type A genetic material.
 M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY SECTION II 181

Viral vaccines Live attenuated vaccines induce humoral and
cell-mediated immunity but have reverted to
virulence on rare occasions. Killed/inactivated
vaccines induce only humoral immunity but
are stable.
Live attenuated—smallpox, yellow fever,
chickenpox (VZV), Sabin’s polio virus,
MMR.
Killed—Rabies, Influenza, Salk Polio, and HAV
vaccines.
Recombinant—HBV (antigen = recombinant
HBsAg), HPV (types 6, 11, 16, and 18).
No booster needed for live attenuated vaccines.
Dangerous to give live vaccines to
immunocompromised patients or their close
contacts.
“Live! One night only! See small yellow
chickens get vaccinated with Sabin’s and
MMR!”
MMR = measles, mumps, rubella (live
attenuated vaccine that can be given to HIV-
positive patients who do not show signs of
immunodeficiency).
SalK = Killed.
RIP Always.

DNA viral genomes All DNA viruses except the Parvoviridae are All are dsDNA (like our cells), except “part-of-
dsDNA. a-virus” (parvovirus) is ssDNA.
All are linear except papilloma, polyoma, and Parvus = small.
hepadnaviruses (circular).

RNA viral genomes All RNA viruses except Reoviridae are ssRNA. All are ssRNA (like our mRNA), except
Positive-stranded RNA viruses: I went to a “repeato-virus” (reovirus) is dsRNA.
RETRO (RETROvirus) TOGA (TOGAvirus)
party, where I drank FLAVored (FLAVIvirus)
CORONA (CORONAvirus) and ate HIPPY
(HEPEvirus) CALIFORNIA (CALIcivirus)
PICKLES (PICOrnavirus).

Naked viral genome Purified nucleic acids of most dsDNA (except poxviruses and HBV) and (+) strand ssRNA
infectivity (≈ mRNA) viruses are infectious. Naked nucleic acids of (−) strand ssRNA and dsRNA viruses are
not infectious. They require enzymes contained in the complete virion.

Virus ploidy All viruses are haploid (with 1 copy of DNA or RNA) except retroviruses, which have 2 identical
ssRNA molecules (≈ diploid).

Viral replication
DNA viruses All replicate in the nucleus (except poxvirus).
RNA viruses All replicate in the cytoplasm (except influenza virus and retroviruses).
182 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

Viral envelopes Naked (nonenveloped) viruses include Naked CPR and PAPP smears.
Calicivirus, Picornavirus, Reovirus, DNA = PAPP; RNA = CPR.
Parvovirus, Adenovirus, Papilloma, and
Polyoma.
Generally, enveloped viruses acquire their
envelopes from plasma membrane when they
exit from cell. Exceptions are herpesviruses,
which acquire envelopes from nuclear
membrane.

DNA virus Some general rules—all DNA viruses:

characteristics
1. Are HHAPPPPy viruses Hepadna, Herpes, Adeno, Pox, Parvo,
2. Are double stranded Papilloma, Polyoma.
3. Are linear EXCEPT parvo (single stranded).
4. Are icosahedral EXCEPT papilloma and polyoma (circular,
5. Replicate in the nucleus supercoiled) and hepadna (circular,
incomplete).
EXCEPT pox (complex).
EXCEPT pox (carries own DNA-dependent
RNA polymerase).
 M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY SECTION II 183

DNA viruses
Viral family Envelope DNA structure Medical importance
Herpesviruses Yes DS – linear HSV-1—oral (and some genital) lesions, spontaneous
temporal lobe encephalitis, keratoconjunctivitis
HSV-2—genital (and some oral) lesions
VZV (HHV-3)—chickenpox, zoster (shingles)
EBV (HHV-4)—mononucleosis, Burkitt’s lymphoma,
Hodgkin’s lymphoma
CMV (HHV-5)—infection in immunosuppressed
patients (AIDS retinitis), especially transplant
recipients; congenital defects (SIGHT-omegalovirus)
HHV-6—roseola (exanthem subitum)
HHV-7--clinically insignificant (included only to
complete family)
HHV-8—Kaposi’s sarcoma–associated herpesvirus
(KSHV)
Hepadnavirus Yes DS – partial circular HBV
Acute or chronic hepatitis
Vaccine available—contains HBV surface antigen
Not a retrovirus but has reverse transcriptase
Adenovirus No DS – linear Febrile pharyngitis—sore throat; acute hemorrhagic
cystitis
Pneumonia
Conjunctivitis—“pink eye” (watery)
Parvovirus No SS – linear (−) B19 virus—aplastic crises in sickle cell disease,
(smallest DNA virus) “slapped cheeks” rash in children—erythema
infectiosum (fifth disease), RBC destruction in fetus
leads to hydrops fetalis and death, pure RBC aplasia
and rheumatoid arthritis–like symptoms in adults
Papillomavirus* No DS – circular HPV—warts (1, 2, 6, 11), CIN, cervical cancer (16, 18)
vaccine available
Polyomavirus* No DS – circular JC—progressive multifocal leukoencephalopathy
(PML) in HIV
BK virus—transplant patients, commonly targets
kidney
(JC: Junky Cerebrum; BK: Bad Kidney)
Poxvirus Yes DS – linear Smallpox, although eradicated, could be used in germ
(largest DNA virus) warfare
Vaccinia—cowpox (“milkmaid’s blisters”)
Molluscum contagiosum—flesh-colored dome lesions
with central dimple
*Papillomavirus and polyomavirus are two new classifications originally grouped as “papovavirus.”
184 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

Herpesviruses
Virus Diseases Route of transmission
HSV-1 Gingivostomatitis, keratoconjunctivitis, Respiratory secretions, saliva
temporal lobe encephalitis (most common
cause of sporadic encephalitis in the United
States), herpes labialis A . Latent in trigeminal
ganglia.
HSV-2 Herpes genitalis B , neonatal herpes. Latent in Sexual contact, perinatal
sacral ganglia.
VZV Varicella-zoster (chicken pox, shingles) C , Respiratory secretions
encephalitis, pneumonia. Latent in dorsal root
or trigeminal ganglia.
EBV Infectious mononucleosis, Burkitt’s lymphoma, Respiratory secretions, saliva
nasopharyngeal carcinoma. Latent in B cells.
CMV Congenital infection, mononucleosis (negative Congenital, transfusion, sexual contact, saliva,
Monospot), pneumonia, retinitis. Infected urine, transplant
cells have characteristic “owl’s eye” inclusions
D . Latent in mononuclear cells.
HHV-6 Roseola: high fevers for several days that can Not determined
cause seizures, followed by a diffuse macular
rash
HHV-8 Kaposi’s sarcoma (HIV patients) Sexual contact

A Herpes labialis. Grouped and confluent vesicles with an

erythematous rim. B Herpes genitalis. Ulcerating vesicles associated with
HSV-2.

C Zoster. Hemorrhagic vesicles and pustules in dermatomal

distribution. D CMV. Renal tubular cells in a neonate with congenital CMV
infection. Note the “owl-eye” inclusions (arrows).
 M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY SECTION II 185

HSV identification Tzanck test—a smear of an opened skin vesicle Tzanck heavens I do not have herpes.
to detect multinucleated giant cells. Used to
assay for HSV-1, HSV-2, and VZV.
Infected cells also have intranuclear Cowdry A
inclusions.

EBV A herpesvirus. Can cause mononucleosis. Most common during peak kissing years (“kissing
Infects B cells. Characterized by fever, disease”).
hepatosplenomegaly, pharyngitis, and
lymphadenopathy (especially posterior cervical
nodes). Peak incidence 15–20 years of age.
Atypical lymphocytes seen on peripheral blood
smear A are not infected B cells but rather
reactive cytotoxic T cells.
Positive Monospot test—heterophile antibodies
detected by agglutination of sheep or horse
RBCs. Also associated with development of
Hodgkin’s and endemic Burkitt’s lymphomas
as well as nasopharyngeal carcinoma.

A Atypical lymphocytes. Seen with EBV infection. Note

“hugging” of RBCs (arrow).
186 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

RNA viruses
Capsid
Viral family Envelope RNA structure symmetry Medical importance
Reoviruses No DS linear Icosahedral Coltivirus—Colorado tick fever
10–12 segments (double) Rotavirus—#1 cause of fatal diarrhea in children
Picornaviruses No SS + linear Icosahedral Poliovirus—polio-Salk/Sabin vaccines—
IPV/OPV
Echovirus—aseptic meningitis
Rhinovirus—“common cold”
Coxsackievirus—aseptic meningitis
herpangina—febrile pharyngitis hand, foot,
and mouth disease myocarditis
HAV—acute viral hepatitis
Hepevirus No SS + linear Icosahedral HEV
Caliciviruses No SS + linear Icosahedral Norwalk virus—viral gastroenteritis
Flaviviruses Yes SS + linear Icosahedral HCV
Yellow fever*
Dengue*
St. Louis encephalitis*
West Nile virus*
Togaviruses Yes SS + linear Icosahedral Rubella (German measles)
Eastern equine encephalitis*
Western equine encephalitis*
Retroviruses Yes SS + linear Icosahedral Have reverse transcriptase
(HTLV), HIV—AIDS
complex HTLV—T-cell leukemia
and conical
(HIV)
Coronaviruses Yes SS + linear Helical Coronavirus—“common cold” and SARS
Orthomyxoviruses Yes SS − linear Helical Influenza virus
8 segments
Paramyxoviruses Yes SS − linear Helical PaRaMyxovirus:
Nonsegmented Parainfluenza—croup
RSV—bronchiolitis in babies; Rx—ribavirin
Rubeola (Measles) Mumps
Rhabdoviruses Yes SS − linear Helical Rabies
Filoviruses Yes SS − linear Helical Ebola/Marburg hemorrhagic fever—often fatal!
Arenaviruses Yes SS − circular Helical LCMV—lymphocytic choriomeningitis virus
2 segments Lassa fever encephalitis—spread by mice
Bunyaviruses Yes SS − circular Helical California encephalitis*
3 segments Sandfly/Rift Valley fevers*
Crimean-Congo hemorrhagic fever*
Hantavirus—hemorrhagic fever, pneumonia
Deltavirus Yes SS − circular Helical HDV
SS, single-stranded; DS, double-stranded; +, + sense; −, − sense; *= arbovirus, transmitted by arthropods (mosquitoes, ticks).
(Adapted, with permission, from Levinson W, Jawetz E. Medical Microbiology and Immunology: Examination and Board Review, 6th ed. New York: McGraw-Hill, 2000: 182.)
 M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY SECTION II 187

Negative-stranded Must transcribe negative strand to positive. Always Bring Polymerase Or Fail Replication.
viruses Virion brings its own RNA-dependent RNA
polymerase. They include Arenaviruses,
Bunyaviruses, Paramyxoviruses,
Orthomyxoviruses, Filoviruses, and
Rhabdoviruses.

Segmented viruses All are RNA viruses. They include BOAR.

Bunyaviruses, Orthomyxoviruses (influenza
viruses), Arenaviruses, and Reoviruses.

Picornavirus Includes Poliovirus, Echovirus, Rhinovirus, PicoRNAvirus = small RNA virus.

Coxsackievirus, HAV. RNA is translated into PERCH on a “peak” (pico).
1 large polypeptide that is cleaved by proteases
into functional viral proteins. Can cause
aseptic (viral) meningitis (except rhinovirus
and HAV). All are enteroviruses (fecal-oral
spread) except rhinovirus.

Rhinovirus A picornavirus. Nonenveloped RNA virus. Rhino has a runny nose.

Cause of common cold; > 100 serologic types.
Acid labile—destroyed by stomach acid;
therefore, does not infect the GI tract (unlike
the other picornaviruses).

Yellow fever virus A flavivirus (also an arbovirus) transmitted Flavi = yellow, jaundice.
by Aedes mosquitos. Virus has a monkey or
human reservoir.
Symptoms: high fever, black vomitus, and
jaundice.

Rotavirus Rotavirus, the most important global cause ROTA = Right Out The Anus.
of infantile gastroenteritis, is a segmented
dsRNA virus (a reovirus). Major cause of acute
diarrhea in the United States during winter,
especially in day-care centers, kindergartens.
Villous destruction with atrophy leads to ↓
absorption of Na+ and water.
188 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

Influenza viruses Orthomyxoviruses. Enveloped, negative single- Killed viral vaccine is major mode of protection;
stranded RNA viruses with 8-segment genome. reformulated vaccine offered each fall.
Contain hemagglutinin (promotes viral
entry) and neuraminidase (promotes progeny
virion release) antigens. Patients at risk for
fatal bacterial superinfection. Rapid genetic
changes.
Genetic shift / Reassortment of viral genome; segments Sudden Shift is more deadly than graDual Drift.
antigenic shifts undergo high-frequency recombination, such
(pandemic) as when human flu A virus recombines with
swine flu A virus.
Genetic drift Minor (antigenic drift) changes based on
(epidemic) random mutation.

Rubella virus A togavirus. Causes rubella, once known as German (3-day) measles. Fever, postauricular
adenopathy, lymphadenopathy, arthralgias, fine truncal rash that starts at head and moves down.
Causes mild disease in children but serious congenital disease (a TORCH infection).

Paramyxoviruses Paramyxoviruses cause disease in children. They include those that cause parainfluenza (croup:
seal-like barking cough), mumps, and measles as well as RSV, which causes respiratory tract
infection (bronchiolitis, pneumonia) in infants. All contain surface F (fusion) protein, which
causes respiratory epithelial cells to fuse and form multinucleated cells. Palivizumab (monoclonal
antibody against F protein) prevents pneumonia in premature infants.
 M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY SECTION II 189

Measles (rubeola) virus A paramyxovirus that causes measles. 3 C’s of measles:

Koplic spots A , red spots with blue-white Cough
center on buccal mucosa, and descending Coryza
maculopapular rash B are characteristic. Conjunctivitis
SSPE (years later), encephalitis (1:2000),
and giant cell pneumonia (rarely, in
immunosuppressed) are possible sequelae.
Rash presents last and spreads from head
to toe. Includes hands and feet (vs. truncal
rash in rubella). Do not confuse with roseola
(caused by HHV-6).

A Koplik spots. Note small white lesions with an erythema-

tous halo that precede the measles rash by 1-2 days. B Rash of measles. Discrete erythematous rash becomes
confluent as it progresses downward.

Mumps virus A paramyxovirus.

Symptoms: Parotitis, Orchitis (inflammation
of testes), and aseptic Meningitis. Can cause
sterility (especially after puberty).
Mumps makes your parotid glands A and testes
as big as POM-poms.

A Mumps. Swollen neck and parotid glands (arrows).

190 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

Rabies virus Has bullet-shaped capsid A . Negri bodies Travels to the CNS by migrating in a retrograde
A are characteristic cytoplasmic inclusions in fashion up nerve axons.
neurons infected by rabies virus; commonly
found in Purkinje cells of cerebellum B .
Rabies has long incubation period (weeks to
months) before symptom onset. However,
prophylactic vaccination should occur
immediately upon exposure.
Progression of disease: fever, malaise →
agitation, photophobia, hydrophobia →
paralysis, coma → death.
More commonly from bat, raccoon, and skunk
bites than from dog bites in the United States.

B Negri bodies.

Hepatitis viruses
Virus Transmission Carrier Incubation HCC risk Notes
HAVa RNA Fecal-oral No Short (weeks) No Asymptomatic
picornavirus (usually), Acute,
Alone (no
carriers)
HBV b DNA Parenteral, Yes Long (months) Yes: may act as
hepadnavirus sexual, oncogene
maternal-
fetal
HCV RNA flavivirus Primarily Yes Long Yes: may be Chronic,
blood, from chronic Cirrhosis,
IVDU, post- inflammation Carcinoma,
transfusion Carrier
HDV RNA delta virus Parenteral, Yes Defective virus that Depends on HbsAg as envelope;
sexual, coinfect or superinfect (worse prognosis)
maternal-
fetal
HEVa RNA hepevirus Fecal-oral, No Short No High mortality
especially in pregnant
with women; Enteric,
waterborne Expectant
epidemics mothers,
Epidemic
Signs and symptoms of all hepatitis viruses: episodes of fever, jaundice, elevated ALT and AST.
aHAV and HEV are fecal-oral: The vowels hit your bowels. Naked viruses do not rely on an envelope so they are not destroyed

by the gut.
bIn HBV, cellular RNA polymerase transcribes RNA from DNA template. Reverse transcriptase transcribes RNA intermediate

into DNA genome. The virion enzyme is a DNA-dependent DNA polymerase.

 M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY SECTION II 191

Hepatitis serologic markers

Anti-HAVAb (IgM) IgM antibody to HAV; best test to detect active hepatitis A.
Anti-HAVAb (IgG) IgG antibody indicates prior HAV infection; protects against reinfection.
HBsAg Antigen found on surface of HBV; indicates hepatitis B infection.
Anti-HBsAg Antibody to HBsAg; indicates immunity to hepatitis B.
HBcAg Antigen associated with core of HBV.
Anti-HBcAg Antibody to HBcAg; IgM = acute/recent infection; IgG = chronic disease. Positive
during window period.
HBeAg A second, different antigenic determinant in the HBV core. HBeAg indicates active
viral replication and therefore high transmissibility.
Anti-HBeAg Antibody to e antigen; indicates low transmissibility.

Important diagnostic tests

Incubation Prodrome, Convalescence
period acute disease Early Late
HBsAg Anti- Anti-HBs
HBsAg
(anti-HBc) HBc (anti-HBc)
Coat protein
(HBsAg)
0 1 2 3 4 5 6 7 8
Core (HBcAg)
42 DNA polymerase
nm DNA genome
(–) (+) HBV particles Anti-HBc

DNA polymerase
Titer

HBsAg
Virus particle

Window period Anti-HBs

HBeAg
In viral hepatitis, ALT > AST. Anti-HBe
In alcoholic hepatitis, AST > ALT. Level of
SECES: SE are antigens, CES direction
are antibodies; labeled in order
of appearance. 0 1 2 3 4 5 6 7 8
Months after exposure

HBsAb Anti-HBsAb HBeAg Anti-HBeAb Anti-HBcAb

Acute HBV + + IgM
Window +
Chronic HBV (high infectivity) + + IgG
Chronic HBV (low infectivity) + + IgG
Recoveray + + IgG
Immunized +
192 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

HIV

Envelope proteins; acquired through budding from host cell plasma membrane Diploid genome (2 molecules of RNA).
The 3 structural genes (protein coded for):
gp120 env (gp120 and gp41)
Docking Formed from cleavage of gp160 to form
glycoprotein envelope proteins
Lipid gp120—attachment to host T cell
RNA
gp41
membrane gp41—fusion and entry
Transmembrane Capsid gag (p24)—capsid protein
glycoprotein
Matrix pol—reverse transcriptase
Capsid protein: p24
Matrix protein: p 17 Reverse transcriptase synthesizes dsDNA from
RNA; dsDNA integrates into host genome.

Reverse
transcriptase

Virus binds CXCR4 or CCR5 co-receptor and CD4 on T cells; binds CCR5 and CD4 on macrophages. Homozygous CCR5
mutation = immunity. Heterozygous CCR5 mutation = slower course.

HIV diagnosis Presumptive diagnosis made with ELISA ELISA/Western blot tests look for antibodies
(sensitive, high false-positive rate and low to viral proteins; these tests are often falsely
threshold, RULE OUT test); positive results negative in the first 1–2 months of HIV
are then confirmed with Western blot assay infection and falsely positive initially in babies
(specific, high false-negative rate and high born to infected mothers (anti-gp120 crosses
threshold, RULE IN test). placenta).
HIV PCR/viral load tests are increasing in
popularity: they allow physician to monitor the
effect of drug therapy on viral load.
AIDS diagnosis ≤ 200 CD4+ (normal: 500–
1500). HIV positive with AIDS indicator
condition (e.g., Pneumocystis jiroveci
pneumonia, formerly known as PCP) or CD4/
CD8 ratio < 1.5.
 M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY SECTION II 193

Time course of HIV infection

4 stages of infection: ±Acute HIV syndrome
Wide dissemination of virus
1. Flulike (acute) Opportunistic
Seeding of lymphoid organs
2. Feeling fine (latent) diseases
3. Falling count Primary
infection Constitutional
4. Final crisis 1200 108
symptoms
During latent phase, virus 1100
replicates in lymph nodes. 1000 107
900 Clinical latency
800 106
700
Death
600 105
500
400 104
300
200 103
100
0 102
0 1 2 3 1 2 3 4 5 6 7 8 9 10 11
Months Years

Red line = CD4+ T lymphocyte count (cells/mm3); blue line = HIV RNA copies per mL
plasma.
194 SECTION II M IC ROBIOLOGY MICROBIOLOGY—VIROLOGY

Common diseases of As CD4 count ↓, risk of reactivation of past infections (e.g., TB, HSV, shingles), dissemination
HIV-positive adults of bacterial infections and fungal infections (e.g., coccidioidomycosis), and non-Hodgkin’s
lymphomas ↑.
Clinical presentation Findings/labs Pathogen
Systemic
Low-grade fevers, cough, Oval yeast cells within macrophages, CD4 < 100 Histoplasma capsulatum (causes only pulmonary
hepatosplenomegaly, symptoms in immunocompetent hosts)
tongue ulcer
Dermatologic
Fluffy white cottage- Pseudohyphae, commonly oral if CD4 < 400, C. albicans (causes thrush)
cheese lesions esophageal if CD4 < 100
Superficial vascular Biopsy reveals neutrophilic inflammation Bartonella henselae (causes bacillary
proliferation angiomatosis)
Gastrointestinal
Chronic, watery Acid-fast cysts seen in stool especially when CD4 Cryptosporidium spp.
diarrhea < 200
Neurologic
Encephalopathy Due to reactivation of a latent virus; results in JC virus reactivation (cause of PML)
demyelination, CD4 < 200
Abscesses Many ring-enhancing lesions on imaging, CD4 Toxoplasma gondii
< 100
Meningitis India ink stain reveals yeast with narrow-based Cryptococcus neoformans (may also cause
budding and large capsule, CD4 < 50 encephalitis)
Retinitis Cotton-wool spots on funduscopic exam and CMV
may also occur with esophagitis, CD4 < 50
Dementia Must differentiate from other causes Directly associated with HIV
Oncologic
Superficial neoplastic Biopsy reveals lymphocytic inflammation HHV-8 (causes Kaposi’s sarcoma), do not
proliferation of confuse with B. henselae
vasculature
Hairy leukoplakia Often on lateral tongue EBV
Non-Hodgkin’s Often on oropharynx (Waldeyer’s ring) May be associated with EBV
lymphoma (large cell
type)
Squamous cell Often in anus (MSM) or cervix (females) HPV
carcinoma
Primary CNS Focal or multiple, differentiate from Often associated with EBV
lymphoma toxoplasmosis
Respiratory
Interstitial pneumonia Biopsy reveals cells with intranuclear (owl’s eye) CMV
inclusion bodies
Invasive aspergillosis Pleuritic pain, hemoptysis, infiltrates on imaging Aspergillus fumigatus
Pneumonia Especially with CD4 < 200 Pneumocystis jiroveci (formerly carinii)
Tuberculosis-like Especially with CD4 < 50 Mycobacterium avium–intracellulare
disease