MYCOLOGY AND VIROLOGY: PAPILLOMAVIRIDAE 10/10/2017

4) Papillomavirus capsid protein L2 disrupts the membrane of the endosome to release

I. FAMILY PAPILLOMAVIRIDAE viral dsDNA into the nucleus
Papillomavirus are naked, icosahedral viruses
Papillomavirus have circular, dsDNA genome PAPILLOMAVIRUS VIRUS LIFE CYCLE IS TIED TO EPETHELIAL CELL
DIFFERENTIATION:
OUTSTANDING CHARACTERISTICS OF PAPILLOMAVIRUS

Stimulate cell DNA synthesis

Restricted host range and tissue tropism
Significant cause of human cancer, especially cervical cancer
Viral oncoproteins interact with cellular tumor suppressor protein

IMPORTANT PROPERTIES OF PAPILLOMAVIRUSES

VARION: Icosahedral, 55nm in diameter

COMPOSITION: DNA (10%), protein (90%)
GENOME: Double stranded DNA, circular, 8kbp, MW 5 million
PROTEINS: Two structural protein; cellular histones condense DNA in varion Viral nucleic acid can be found in basal stem cell
ENVELOPE: NONE Late gene expression of capsid proteins is restricted to the uppermost layer of
REPLICATION: Nucleus differentiated keratinocytes
OUTSTANDING CHARACTERISTICS: Stimulate DNA synthesis, restricted host range and tissue Viral particles are released from the surface of Papillomatous lesions
tropism, significant cause of human cancer, especially cervical cancer, viral oncoproteins Transmission of HPV occurs by close contact
interact with cellular tumor suppressor proteins Papillomavirus infections lead to the development of different kinds of warts
HPV genital infections are sexually transmitted and represent the most common sexually
PAPILLOMAVIRUS WERE FORMER MEMBERS OF FAMILY PAPOVAVIRIDAE: transmitted disease in the US
Many HPV infections are benign
Separated because of differences in genome organization and biology Nearly all HPV infections are cleared and become undetectable within 2-3 years
Papillomaviruses are slightly larger in diameter (55nm than Polyomaviruses 45nm) HPV type 16 and 18 and other less common type are considered high cancer risk
Papillomavirus contain a larger genome 8kbp vs 5kbp Cervical cancer is the most frequent cancer in women worldwide and is a major cause
The organization of the Papillomavirus genome is more complex of cancer deaths in developing countries
Cervical cancer develops slowly which may take years to decades
PAPILLOMAVIRUSES THAT CAN INFECT HUMANS
TYPES OF HUMAN PAPILLOMAVIRUSES ASSOCIATED WITH CLINICAL
Genus Alphapapillomavirus
LESIONS AND ONCOGENEIC POTENTIAL
Genus Betapapillomavirus
Genus Gammapapillomavirus HUMAN
Genus Mupapapillomavirus PAPILLOMAVIRUS CLINICAL LESIONS SUSPECTED ONCOGENIC POTENTIAL
Genus Nupapapillomavirus TYPES
1 Plantar warts Benign
REPLICATION OF PAPILLOMAVIRUSES
the papillomaviruses are highly trophic for the epithelial cells of the skin and 2, 4, 27, 57 Common skin Benign
mucus membrane: warts
3, 10, 28, 49, Cutaneous Low
1) Papillomaviruses gain access to keratinocytes, stem cells through small wounds or 60, 76, 78 Lesions
microtraumas in the skin or mucosal surface 5, 8, 9, 12, 17, Epidermodysplasia Mostly Benign, but some progress to
2) Papillomavirus capsid L1 protein interacts with cell surface, sulfated sugars for 20, 36, 47 verruciformis malignancies
attachment 6, 11, 40, 42- Anogenital Low
44, 54, 61, 70, Condylomas,
3) Papillomavirus penetrates the cell through Alpha6 Beta 4 integrin through endosomes
72, 81 Layngeal
Papillomas;
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MYCOLOGY AND VIROLOGY: PAPILLOMAVIRIDAE 10/10/2017

Dysplasia, Approved in the US in 2006

Intraepithelial
neoplasia or B. BIVALENT HPV VACCINE:
mucosal sites Contains particles from HPV types 26 and 18
7 Hand warts of Low Approved in the US in 2007
butchers Both vaccines are effective at preventing persistent infections by the targeted HPV types
16, 18, 30, 31, High grade High correlation with genital and oral and the development of HPV related genital precancerous lesions
33, 35, 39, 45, dysplasia and carcinoma , esp cervical cancer Both vaccines are not effective against established HPV disease
51-53, 56, 58, carcinomas of It is not known how long vaccine-induced immunity lasts, but it appears to extend for at
59, 66, 68, 73, genital mucosa, least 5 years
82 Laryngeal HPV vaccines are not recommended for pregnant females
Esophangeal
carcinoma
II. FAMILY RETROVIRIDAE
(Insert Graph Picture)
Retroviruses contains an RNA genome and an RNA directed DNA polymerase (reverse
CLINICAL FINDINGS AND EPIDEMIOLOGY OF HPV INFECTION: transcriptase)

Retroviruses are enveloped virus with complex capsid symmetry: Retroviruses contain a
HPV is the most common viral infection of the reproductive tract
helical nucleocapsid within an icosahedral capsid
An estimated 660 million people worldwide have HPV genital infections
Retroviruses have diploid (+) ssRNA
Peak incidence of HPV infections occurs in adolescence and young adult under 25 yrs of
age
IMPORTANT PROPERTIES OF RETROVIRUS
HPVs are the accepted cause anogenital cancers
Over 99% of cancers and 80% of anal cancers are linked to HPV genital infections VARION: spherical, 80-110 nm in diameter, helical
nucleoprotein within icosahedral capsid
COMPOSITION: RNA (2%), protein (about 60%),
HPV-16 AND HPV 18
lipid (about 35%), carbohydrate (about 3%)
Responsible for more than 70% of all cervical cancers than HPV 18 GENOME: Single stranded RNA, linear, 8kbp,
HPV 16 cause most cervical cancers than HPV 18 positive sense, 7-11 kb, diploid; may be
HPV 16 is also linked to oropharyngeal cancer than HPV 18 defective; may carry oncogene
PROTEINS: reverse transcriptase enzyme
HPV 6 AND HPV 11
contained inside virions
ENVELOPE: present
RESPONSIBLE FOR:
REPLICATION: reverse transcriptase makes DNA
90% of anogenital warts copy from genomic RNA; DNA (provirus)
Laryngeal papillomas in children: recurrent respiratory papillomatosis integrates into cellular chromosome; provirus is
Benign genital condylomas template for viral RNA
There is a high prevalence of HPV DNA in normal skin from healthy adults MATURATION: Virion bud from plasma membrane
These asymptomatic HPV infections are acquired early in infancy OUTSTANDING CHARACTERISTICS:
There is increased incidence of warts and cervical cancers in immunosuppressed pxs Infections do not kill cells
All HPV associated cancers occur more frequently in persons with HIV/AIDS
May transduce cellular oncogenes, may activate expression of cell genes
PREVENTION AND CONTROL OF HPV Proviruses remain permanently associated with cells and are frequently not
expressed
Non-infectious recombinant HPV vaccines: Many members are tumor viruses

A. QUADRIVALENT HPV VACCINE:

Contains particles derived from HPV types 6,11,16,18

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MYCOLOGY AND VIROLOGY: PAPILLOMAVIRIDAE 10/10/2017

CLASSIFICATION OF RETROVIRUSES F. ONCOGENIC POTENTIAL

A. BY GENERA
RETROVIRUSES THAT CARRY ONCOGENES:
A. GENUS ALPHARETROVIRUS Avian leucosis and sarcoma viruses
Highly oncogenic
B. GENUS BETARETROVIRUS Mouse mammary tumor virus Sometimes referred to as acute transforming agents: rapidly induce morphologic
C. GENUS GAMMARETROVIRUS Mammalian leukemia and sarcoma viruses transformation of cells in vitro, induce tumors in vivo after very short latent period
Human T-lymphoctropic viruses (HTLV) and RETROVIRUSES THAT DO NOT CARRY ONCOGENES:
D. GENUS DELTARETROVIRUS
bovine leukemia virus Have a much lower oncogenic potential
E. GENUS EPSILONRETROVIRUS Fish viruses Sometimes referred to as slow transforming agents:
Contains viruses able to cause foamy Disease usually of blood cells appears after a long latent period
F. GENUS SPUMAVIRUS degeneration of inoculated cells which are not Cultured cells are not transformed
associated with any known disease process
G. GENUS LENTIVIRUS HIV
REPLICATION OF RETROVIRUSES
B. BY HOST OF ORIGIN Replication of Retroviruses involves both cutoplasm
Retrovirus have been isolated from all vertebrate species and nucleus of host cells
Retroviruses are generally not cytolytic
Infections across species may occur Lentiviruses are cytolytic
1. Attachment of retrovirus to cell receptor:
C. EXOGENOUS OR ENDOGENOUS
HTLV attaches to GLUT-I receptor
EXOGENOUS- spread horizontally
HIV attaches to CD4
ENDOGENOUS- spread vertically
2. Viral capsid goes into cytoplasm of cell
3. Viral reverse transcriptase produces a DNA copy of
D. BY HOST RANGE viral genome in capsid
4. Viral DNA is integrated into cell DNA to form
Infect and replicate only in cells from animals
ECOTROPIC VIRUSES of the original host species Provirus
5. Provirus serves as template for synthesis of viral
Able to infect cells of the natural host and of
AMPHOTROPIC VIRUSES heterologous species transcripts:
Can replicate in some heterogeneous a. Spliced viral transcripts become viral
or foreign cells but not in cells of the mRNA
XENOTROPIC VIRUSES natal host
Many endogenous viruses have b. Unspliced viral transcripts become
xenotropic host range viral RNA
6. Viral mRNA is translated to viral proteins
E. GENETIC CONTENT 7. Viral proteins assemble with viral RNA in cell
Retroviruses have simple genetic content cytoplasm
Lentiviruses including HIV have more complex genome and contain several additional 8. Viral particles bud off from the cell
accessory genes

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GENUS LENTIVIRUS PATHOGENISIS OF HIV INFECTION

Lentivirus have been isolated from many species including African nonhuman primate 1. HIV attaches to the CD4 receptor on macrophages and T lymphocytes
species CO-receptors are the chemokine receptors:
CCR5 for macrophage-tropic strains of HIV-1
There are two distinct types of human AIDS viruses:
CXCR4 for lymphocyte-tropic strains of virus
HIV-1 and HIV-2
2. HIV inserts and integrates its RNA into the DNA of macrophages and T lymphocytes
HIV-I and HIV-2 are distinguished on the basis of genome organization and phylogenetic 3. Infected macrophage and T lymphocytes replicate HIV
(evolutionary) relationships with other primate lentivirus 4. Infected macrophages and T lymphocytes are destroyed and can no longer send signals
HIV in human originated from cross-species infections by simian virus in rural Africa, to other immune cells of the body
probably due to direct human contact with infected primate blood (Insert chart)

(Insert table 44-2) ORIGIN OF HIV-1 Cross species transmission of SIVcpz

ANIMAL LENTIVIRUS SYSTEM ORIGIN OF HIV-2 Cross-species transmission SIVsm

Natural disease pattern vary among species, but certain common features are WHAT ARE CD4 CELLS
recognized:
CD4 cells are cells with CD4 receptors
1. Viruses are transmitted by exchanged of body fluids CD4 is a protein found on the surface of lymphocytes, monocytes, macrophages, and
2. Virus persist indefinitely infected host, although it may be present at very low levels dendritic cells
Surface of T-helper lymphocytes has a lot of CD4 receptors
3. Viruses have high mutation rates and different mutants will be selected under different T-helper lymphocytes play a role in activating other immune cells of the body in the
condition presence of infectious etiologic agents
CD4 cells (T cells) send signals to activate your bodys immune response when they
4. Virus infection progresses slowly through specific stages detect intruders like viruses or bacteria
NORMAL VALUES:
5. It may take years for disease to develop
In a healthy adult, a normal CD4 cell count can vary a great deal
HIV INFECTION IN HUMAN Typically 500 to 1500 cells per cubic millimeter of blood
Typical course of untreated HIV infection spans about a decade
WHAT HAPPENS IF THERE ARE LESS THAN 200 CD4 CELLS PER CUBIC
Stages of HIV infection in Humans:
a. Primary infection MILLIMETER OF BLOOD?
b. Dissemination of virus to lymphoid organs Immune system is severely wakened
c. Clinical latency
Patient is at much greater risk of opportunistic infections
d. Elevated HIV expression
e. Clinical disease Among the criteria for and HIV positive person to be classified as having AIDS
f. Death AIDS (Acquired Immunodeficiency Syndrome)
Symptoms of acute HIV infection are non-specific Acquired-not inherited, but may be passed on from infected mother to child during
Duration between primary infection and progression to clinical disease is about 10 years pregnancy and through breast milk
In untreated cases, death usually occurs within 2 years after onset of clinical symptoms Immune-affects the bodys immune system particularly CD4 T-lymphocytes
Deficiency- the immune system is deficient or isnt working the way it should
Syndrome- a collection of signs and symptoms of disease

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Aids is a syndrome, rather than a single disease, because it is a complex illness with a wide range of However, levels of neutralizing activity are low
complication Many anti-envelope antibodies are non-neutralizing

AIDS IS THE FINAL STAGE OF HIV INFECTION VIRAL ENVELOPE GLYCOPROTEIN SHOWS GREAT VARIABILITY

Not everyone who has HIV advances to AIDS This natural variation may allow the evolution of successive populations of resistant
people with AIDS have badly damage immune system, which put them at risk for
virus that escape recognition by existing neutralizing antibodies
opportunistic infections
It is not clear which host responses are important in providing against HIV infection or
PATIENTS ARE CONSIDERED PROGRESS TO AIDS IF ANY IS PRESENT: development of disease
There is one or many opportunistic infection
Certain cancer ROUTES OF TRANSMISSION
A very low number of CD4 cells
High titers of HIV are found in blood and semen
If a patient is progress to aids the patient need medical intervention and treatment to prevent death
HIV is transmitted during sexual contact, through parenteral exposure to contaminated
LABORATORY DIAGNOSIS OF HIV blood or blood products, and from mother to child during perinatal period
1. Virus Isolation
(INSERT PICTURE)
2. Serologic Determination of Anti-viral antibodies
3. Measurement of viral nucleic acid or antigens
EPIDEMIOLOGY, PREVENTION, TREATMENT AND CONTROL OF HIV/AIDS
HIV infected persons develop both humoral and cell mediated responses against HIV
related antigens EPIDEMIOLOGY OF HIV/AIDS
Antibodies to a number of viral antigens develops soon after infection

PEOPLE LIVING WITH HIV/AIDS MORTALITY

MAJOR GENE PRODUCT OF HIV THAT ARE USEFUL IN DIAGNOSIS OF
36.7 million 1.1 million
INFECTION
People died of AIDS related illnesses worldwide
GENE PRODUCT DESCRIPTION People living with AIDS worldwide in 2015
in 2015
gp 160b Precursor of envelope glycoproteins
gp 120b Outer envelope glycoproteins of virion, SUc
(INSERT PICTURE)
p66 Reverse transcriptase and RNAse H from polymerase gene product
p55 Precursors of core protein, polyprotein from gag gene VACCINES AGAINST HIV

p51 Reverse transcriptase, RT

ALL CANDIDATE HIV VACCINES TESTED AS OF 2011 PROVE INEFFECTIVE OR POORLY EFFECTIVE AT PREVENTING
gp 41b Transmembrane envelope glycoprotein, TM
INFECTIONS
p32 Integrase, IN
p24 b Nucleocapsid core protein of virion, CA VACCINE DEVELOPMENT IS DIFFICULT BECAUSE:

p17 Matrix core protein of virion, MA

HIV mutates rapidly
(insert graph)
HIV is not expressed in all cells that are infected

Most infected individual make neutralizing antibodies against HIV directed against the HIV is not completely cleared by the host immune response after primary infection

envelope glycoprotein
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HIV isolates show marked variation, esp in enveloped antigen. Variability may promote
the emergence of neutralization resistant mutants

THERAPY FOR HIV/AIDS

Antiretro viral therapy (ART) keeps the level of HIV in the body controlled and low
ART involves taking a combination of HIV medicines everyday
HIV medicines can control the virus so that patients can live longer, healthier lives and
reduce the risk of transmitting HIV to others
Today, a person who is diagnose with HIV and treated with disease is far advanced can a
have nearly normal life expectancy
No safe and effective cure for HIV currently exist, but scientists are working hard to
find one, and remain hopeful

OTHER METHODS OF PREVENTING THE SPREAD OF HIV

Topical microbicides containing antiviral drugs show promise as a means of blocking

sexual transmission of HIV
Safe sexual practices control measures
Health education

SUMMARY OF SEXUALLY TRANSMITTED VIRUSES

Sexually transmitted viruses includes Papillomaviruses and HIV

Papillomaviruses and HIV are also considered as cancer agents
HIV infection cause immune suppression
HIV is Lentivirus, a type of Retrovirus
HIV 1 and HIV 2 were derived from primate lentiviruses common in Africa
HIV is transmitted during sexual contact through parenteral exposure to contaminated
blood or blood products, and from mother to child during the perinatal period
Individuals infected with HIV remain infected for life
The amount of HIV in the blood (viral load) is of prognostic value and is crucial for
monitoring effectiveness of drug therapy
HIV drugs can be used for prevention of infection
There is currently no HIV vaccine available

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