BIOL 2421 Microbiology             Lecture Notes: Viruses, Retrovirus HIV and AIDS                 Dr. Weis


     Linear, 2 ss + RNA, linked by Hydrogen bonds

            Also contains a 3rd type of nucleic acid: a specific type of tRNA (trp, pro, or lys)

     Spherical, slightly pleomorphic

     Phospholipid Envelope with spikes

     Contains enzyme, Reverse transcriptase that transcribes vRNA to vDNA to be incorporated into host cell.

            7 Genera of Retroviridae:

                        Gammaretrovirus: mouse mammary tumor (MMT)

                        Episilonretrovirus: reptile virus (MLV)

                        Alpharetrovirus: Avian leucosis (ALV)

                        Betaretrovirus: Monkey virus (MPMV)

                        Deltaretrovirus: Bovine leukemia (BLV); HTLV

                        Spumavirus: chimpanzee, human spumavirus (Foamy cell leukemia)



                                    Bovine Lentivirus group: Bovine immunodeficiency virus (BIV)

                                    Equine Lentivirus group: Equine Infectious Anemia (EIA)

                                    Feline Lentivirus group: Feline immunodeficiency virus (FIV)

                                    Ovine/Caprine  Lentivirus group: Arthritis (CAEV)

                                    Primate Lentivirus group: HIV-1, HIV-2

                                                Human HIV possibly evolved from viruses that affected

                                                African monkeys.  Transition probably around 1930’s.

                                                Earliest known infection 1959 in Congo.

                                                In U.S, 1981.

                                         HIV-1 has 11 clades [branches or subtypes; examples A-H, O]

                                                HIV-1 B is in the US

                                                HIV-1 C is in Africa

                                                HIV-1 E is in Asia

      Lentivirus diseases

            * Immunodeficiency

            * Slow, progressive wasting disorders

            * Allow for opportunistic infections

            * Neurodegeneration

            * Death

HIV core = RNA genome + Nucleocapsid protein + RT + IN

            The core appears conical / helical inside the capsid

RNA genes for HIV

            3 genes for replication: env, gag, pol

            3 regulatory genes: tat, rev, nef

            3 auxiliary genes: vif, vpr, vpu

All retroviruses have 5’-gag – polenv – 3’

        Gag and pol genes are translated into a single protein molecule which is cleaved by viral proteases into

                        * capsid proteins

                        * protease

                        * RT

                        * integrase

        Env genes are translated into an envelope protein, gp 160 which is then cleaved by host proteases into

                        * Surface glycoprotein

                        * Transmembrane glycoprotein

HIV retrovirus has:  5’ – cap –R-U5-PBS-leader -gag-pol-env -ppt- U3- R - 3’

Generalized structure of retrovirus






Matrix [p17]

Gag gene

Creates a continuous inside membrane protein that lines the envelope


Capsid [p24]

Gag gene

Capsid protein that protects the core



[p 9, 6]

Gag gene

Forms the core, helical in appearance


Protease [p11], [p9]

Gag gene

Cleaves protein during maturation


Reverse transcriptase

[p51 and p 66]

Pol gene

Transcribes vRNA genome to make vDNA


Integrase, [p32]

Pol gene

Integration of provirus


Surface glycoprotein

 [gp 120]

env gene

Major antigen in outer envelope, receptor binding to CD4 cells, linked to TM.

Avoids immune cells by changing shape. Also, most of protein is hidden


Transmembrane protein [gp 41]

env gene

Holds SU in envelope, responsible for membrane fusion after initial receptor binding with gp 120

Outer shell = Viral Envelope that is derived from a host Plasma Membrane which is acquired when the virus buds through the cell membrane composed of host cell constituents with viral proteins as spikes.

                        Contains env = cap + stem

                        Glycoproteins (gp)

                                    Cap   = gp 120 is attached to the stem

                                    Stem = gp 41   that transverses the envelope

Within the viral envelope is a matrix protein (p): p17

                        Matrix protein is icosahedral

                        Functions to

                                    ^ Anchor Transmembrane envelope protein

                                    ^ Assist in viral penetration

                                    ^Transport proviral integration complex across nuclear envelope

                                    ^Localizes assembly of virion to the cell receptor

Within the matrix is a viral core (capsid) is a core antigen protein, p24

Within the capsid is

                        RNA + proteins

                        Integrase, p 32

                        Reverse transcriptase, p51 and p66

                        tRNA lys 3, which acts as an RT primer by binding to its complementary

                                    site on the viral RNA and initiating reverse transcription

Vpu: Viral protein U that enhances virus particle release from infected cells and induces the degradation of CD4.

Vpr: Viral protein R that changes ion channel activity and promotes nuclear entry of viral RNA. Also causes G2 cell cycle arrest that leads to cell death

Protease: Hydrolytic enzyme associated with RNA, critical for viral replication. Important in early step of replication to assemble immature form of virus. Also helps to form mature virus as it is used to cut the long protein pieces into their proper size peptides to make functional protein products that are essential for viral assembly.

Nef: negative factor

            * Interacts with host cell signal transduction proteins to allow long term survival                            of virus in infected T cells by binding to cellular protein kinases

            * Causes the destruction of non-infected cells by inducing apoptosis

            * Advances endocytosis of surface receptors (downgrades CD4 proteins & MHC)

                        to impair T-cytoxic cells to evade host immune system response

            * Renders resting T lymphocytes highly permissive to HIV-1 infection by

                        interacting with the CD40L receptor signaling pathway

            * Contributes to the progression of AIDS

Integrase: helps cut host DNA regions in order to allow integration of vDNA into host cell genome.

Retrovirus Replication

            Attachment: SU envelope protein [gp 120] binds to host target cell receptor, CD4

                                 HIV also infects macrophages to inhibit phagocytosis of IgG and

                                                Complement opsonized pathogens

                                 Second binding to co-receptors

                                     surface chemokine, CCR5 on macrophages in the early stages

                                     surface chemokine, CXCR4 on T helper cells, in the late stages

                        Co-receptor binding is necessary to cause the change in the fusion protein

            Penetration: TM protein fusion domain revealed, virus fuses

            Partial uncoating of nucleocapsid in cytoplasm

            Genome Replication:

                        Reverse Transcriptase inside nucleocapsid core

                        tRNA carried by the virus serves as a primer

                        RT copies the ss+RNA to form a RNA–DNA hybrid

                        Ribonuclease H (a component of RT) degrades +RNA strand to leave –DNA

                        RT then copies this strand to produce a dsDNA called proviral DNA


                        Catalyzed by Integrase

                        Linear ds DNA is used and ends brought together

                        Proviral DNA takes on a circular form and is incorporated into host genome

                        Provirus is present for lifetime of cell


                        Proviral DNA then serves to create mRNA and new ss+ RNA strands

                        Fresh RNA reenters the cytosol where some are translated by ribosomes

                        HIV may remain as latent virions in vacuoles within the cell

                        Lack of proof reading corrections creates a higher mutation rate

            Viral Protease

                        Cleaving of viral proteins to create functional peptides for virus

            Assembly and Budding

                        Capsid assembly at the plasma membrane

                        Host plasma membrane used to create part of viral envelope

Transmission: aided by Langerhans cells in mucosal epithelial cells and STDs.

            Horizontal: Blood, organ transplants, coitus, blood transfusion, needles, AI

            Vertical: Infected mother to child > breast milk, placenta

            Direct: Infected cell to other cells via fusion

            Rate of HIV infection to clinical AIDS is about 10 years

            NOTE: HIV is present in other fluids (urine, feces, sweat, saliva, tears) but

                        No known transmission.........yet!


     Early Phase
            Primary: flu-like symptoms: fever, sweat, sore throat, diarrhea

    Middle phase

            Sero-conversion in 2-4 weeks post infection

            May be asymptomatic

            Continuous infection

            Decreases life span of CD4 cells as well as destruction

            Replacement efforts decrease

    Late Phase

            Symptoms proceed and progress towards AIDS

                        * constitutional: fever, lymphadenopathy, diarrhea, weight loss

                        * neurological: dementia, myelopathy

                        * immunodeficiency: allows for secondary, opportunistic infections

                                                            destruction: lysis of infected cells [CD4+]

                                                            syncytium formation

                        * rare malignancies: Kapsoi’s sarcoma, lymphoma

Stages of HIV

            Category A: asymptomatic, lymphadenopathy, more severe = increase load

            Category B: beginning of opportunistic infections, rare cancers, diarrhea, fever

            Category C: clinical AIDS, T-h count below 200/cubic mm

                                 Persistant Opportunistic infections

                                    a) Viruses: HSV-1, VZV, EBV

                                    b) Bacteria: TB

                                    c) Fungus: candidia, pneumocystis

                                    d) Protozoans: Microsporidia


     IgG: indicates infection, except in infants exposed from mother, must wait for seroconversion

     ELISA of p24 antigen

     PCR to detect vRNA



     HAART => Highly Active AntiRetroviaral Therapy

       (1) Drugs to decrease viral replication

            ~ Nucleoside analogues

                        Interfers with RT

                                    AZT: Thymidine analog drug lacks 3’ Oxygen, creating DNA                                                            chain termination

                                    Dideoxyinosine, Dideoxycytidine


            ~ Nonnucleoside inhibitors of RT

                        APA : binds to pocket between the  p66 protein of RT, near the polymerase activation sites.



            ~ Protease inhibitors (must be used with AZT)

                                    blocks viral protease so that the proteins needed for assembly cannot

                                    be cleaved from the large protein precursors








        (2) Entry Inhibitors

                Competative inhibitor that interferes with fusion process of gp41 penetration of host plasma membrane.


    NOTE: No vaccine due to rapid mutation rate during reverse transcription of vRNA to DNA

Opportunistic Infections

Pneumocystis carinii

            Most frequent opportunistic infection seen with AIDS

            Produces pneumonia with perihilar infiltrates

            Other symptoms: fever, non-productive cough, dyspnea

            Dx: lavage or biopsy to find P carinii cysts


           Herpes virus; Can cause: pneumonia, retinitis


            M. tuberculosis : granulomatous pulmonary disease

            M. avian complex : affects mononuclear phagocyte system(LN, spleen, Liver, BM)

Fungal Infections

            Candidia: invasive infections in esophagus, URTI, and lung

            Systemic infections: Cryptococcus, Histoplasmosis, Coccidioides.


            Toxoplasmosis : T. gondii à brain to create abscesses

            Crytposporidium, Microsporidium, Isospora à watery diarrhea



                        HSV-1 can involve the GI tract at esophagus and perianal region

                        VZV can involve the skin

Malignant Neoplasms

            Kaposi’s Sarcoma (KS)

                        Reddish, purple patches, plaques or nodules over the skin

            Malignant lymphoma à brain


            Lymphoid interstitial pneumonitis (LIP)

                        Lung condition involving children

                        Interstitial pulmonary infiltrates