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Humans, like other animals, are subject to numerous viral infections mediated by viruses either maintained solely in the host population or in another population of animals with which humans interact. We have seen that two basic patterns occur in the course of virus replication in humans – persistent infections with incomplete virus clearing, and acute infections with efficient virus clearing upon recovery from the acute infection. It might be argued that persistent infections represent associations between virus and host that have stabilized over time, such that the viruses are maintained within the host population without a large negative effect. Conversely, acute infections may involve viruses that have recently moved from a different host. In the case of humans, such viruses may originate from zoonotic infections. While influenza A viruses and hantaviruses are examples that support this model, human rhinoviruses, among others, would not, since there are no known animal reservoirs. These virus groups and some of the symptoms caused by their infections of humans are listed in Table 4.1.

Table 4.1 Some viruses infecting humans.

Family	Genome	Primary Reservoir	How Long Associated with Humans	Virus Type	Acute Disease	Primary Infection	Mortality Rate	Persistent/Latent?	Reactivation	Chronic Disease/Complications
Herpesviridae	DNA	Humans	Ancient	HSV‐1	Facial lesion	Epidermis	Nil	Yes	Frequent at site	Encephalitis (rare)
HSV‐2	Genital lesion	Epidermis	Nil	Yes	Frequent at site	Encephalitis (rare)
VZV	Chickenpox	Epidermis	Nil	Yes	Once	Shingles/disseminated infection upon immune suppression
HCMV	Mononucleosis	Hematopoietic tissue	Nil	Yes	Asymptomatic/infrequent?	Disseminated infection upon immune suppression/retinitis
EBV	Mononucleosis	Lymphoid tissue	Nil	Yes	Asymptomatic/infrequent?	Lymphoma/carcinoma
HHV‐6	Roseola	Lymphoid tissue	Nil	Yes	Asymptomatic/infrequent?	?
HHV‐7	Roseola	Lymphoid tissue	Nil	Yes	Asymptomatic/infrequent?	?
HHV‐8	?	Lymphoid tissue	Nil	Yes	Asymptomatic/infrequent?	Kaposi's sarcoma
Polyomaviridae	DNA	Humans	Ancient	JC	None	Kidney/bladder	Nil	Yes	Infrequent (?) shedding	Encephalitis upon immune suppression
BK	None	Kidney/bladder	Nil	Yes	Infrequent (?) shedding	Kidney infection
Papillomaviridae	DNA	Humans	Ancient	>60 types	Warts	Epidermis	Nil	Yes	Constant shedding at site	Cervical carcinoma (Types 6, 11, 16, and 18)
Adenoviridae	DNA	Humans	Ancient?	>12 types	Mild respiratory	Respiratory tract	Nil	Yes	Infrequent shedding?	?
Poxviridae	DNA	Humans	Recent	Variola	Smallpox	Epidermis	Moderate to high	No	N/A	None
Orthomyxoviridae	RNA	Birds, pigs	Sporadic/current	Influenza A	Influenza	Respiratory tract	Usually low/rarely high	No	N/A	None
Humans	Sporadic/current	Influenza B	Influenza	Respiratory tract	Nil			None
Coronaviridae	RNA	Humans	?	Human coronavirus	Cold	Nasopharynx	Nil	No?	N/A	None
Palm civets	Current	SARS	Acute respiratory failure	Respiratory tract	Moderate to high	No	N/A	None
Picornaviridae	RNA	Humans	Recent?	Poliovirus	None to mild digestive upset	GI tract	Nil	No	N/A	Paralysis
Humans	Recent?	Hepatitis A virus	Hepatitis	Liver	Low	No	N/A	Rare
Humans	?	Rhinoviruses	Cold	Respiratory tract	Nil	No?	N/A	None
Hepeviridae	RNA	Human	?	Hepatitis E	Hepatitis; severe in newborns	Liver	Nil, except pregnant women; moderate in newborns	No	N/A	Rare
Flaviviridae	RNA	Birds	Sporadic/current	West Nile	Encephalitis	Brain	Low	No	N/A	Neurological
Primates	Sporadic/current	Yellow fever	Encephalitis	Brain	Moderate	No	N/A	Neurological
Human	?	Hepatitis C virus	Hepatitis	Liver	Low	Occasional	Chronic hepatitis with no virus shedding	Liver failure/carcinoma
Human	Sporadic/current	Dengue	Fever/joint pain	Leukocytes	Low	No	N/A	Hemorrhagic fever
Human/primate	Sporadic/current	Zika	Fever/joint pain/rash	?	Low	No?	N/A	Neurological, teratogen
Rhabdovirus	RNA	Carnivores	Sporadic/current	Rabies	Encephalitis	Brain	100%	No	N/A	N/A
Togavirus	RNA	Horses	Sporadic/current	Equine encephalitis virus	Encephalitis	Brain	Low	No	N/A	Neurological
Human?	?	Rubella virus (German measles)	Rash	Skin/developing nerve tissue	Nil in adults; severe neurological symptoms in developing fetus	No	N/A	Fetal infection
Paramyxovirus	RNA	Carnivore?	Recent	Measles	Rash	Respiratory tract	Low/moderate	Yes/no	Chronic virus antigen present/no infectious virus	SSPE
Human	?	Mumps	Glandular inflammation	Respiratory tract	Nil	No	N/A	Infertility
?	?	Respiratory syncytial virus	Mild respiratory in adults	Nasopharynx	Nil in adults	Yes	Virus shed from nasopharynx	Infections of newborns
Hepatitis delta	RNA	Human	?	Hepatitis D	Hepatitis	Liver	Usually low, but infection with hepatitis B leads to acute liver failure	Yes	Virus antigen present and infectious in blood	Liver failure
Bunyavirus	RNA	Mosquitoes	?	Lacrosse encephalitis virus	Encephalitis	CNS	Low; more severe for children	No	N/A	None
Rodents	?	Hantavirus	Severe respiratory failure	Respiratory tract	Moderate, especially in young adults	No	N/A	Respiratory failure
Hepadnavirus	RNA/DNA	Human	?	Hepatitis B	Hepatitis	Liver	Low	Yes	Virus antigen present and infectious in blood	Liver failure/carcinoma
Retrovirus/RNA tumor virus	RNA/DNA	Humans	Ancient	Human T‐cell leukemia	None	Lymphoid tissue	Nil?	Yes	Infectious virus shed?	Lymphoma/paraparesis
Retrovirus/lentivirus	RNA/DNA	Chimpanzees/mangabeys	1930 ± 20 years/?	HIV‐1/HIV‐2	None/flu‐like or mononucleosis‐like	Lymphoid tissue	100%	Yes	Infectious virus shed	Immunodeficiency

A number of important human viruses are either asymptomatic or cause relatively mild symptoms of primary infection, which is followed by a stable association between virus and host that lasts as long as the latter lives. During this more or less stable association, some viruses are constantly shed, while persistent infections with others lead to loss of any detectable virus. In the latter case, various types of stress to the host can lead to viral recrudescence (reappearance of infectious virus along with mild or no symptoms) with the potential for virus spread to other individuals.

Notable persistent viruses include the human herpesviruses, human papilloma and related polyoma viruses, human retroviruses, and two completely unrelated viruses – hepatitis B and hepatitis C viruses – whose chronic infection leads to severe liver damage. The details of the replication of these viruses will be covered in later chapters in Part IV; what is important to consider now is that the persistent mode of virus–host interaction is well suited to small groups of wandering related individuals with only occasional contact with other such groups. Virus persistence insures that virus can survive without infecting new individuals for the long life of the human host, yet virus recrudescence insures that there will be opportunities for virus spread at opportune times.

A detailed analysis of the genes of these viruses, especially those originally appropriated from the host, using procedures outlined in Chapter 1 demonstrates both their long association with humans and the considerable evidence for their replicative isolation – again expected for an infectious agent constrained to maintain itself in a small, relatively isolated environment.