virology Flashcards
What sort of sequence does the HTLV-1-related endogenous sequence 1 (HRES-1) on human chromosome 1q42 resemble?
The HRES-1 sequence resembles the human and simian T-cell leukemia/lymphotropic viruses (HTLV-1 /STLV-1). HRES-1 Gag protein shows about 30% homology with HTLV-1 gag p24 and HTLV-2 Gag p24.
Phylogenetic analysis suggests it entered the genome as an exogenous retrovirus into old world primates at position 1q42.
What class of proteins are coded by the Gag retroviral gene?
The Gag gene of retroviruses code for about 700 amino acids which may be cleaved into matrix, capsid, and nucleocapsid proteins.
What sequences are present within the HRES-1 human endogenous retroviral sequence?
The HRES-1 gene structure is controversial as some sequences are suspect. It probably starts with inverted repeats, TAR sequence, then a viral TATA box, then a poly(A) tract flanked by inverted repeats followed by PBS (primer binding site).
Size estimates include:
HRES-1/Alu exon 2 goes from 320-627, then the 78 poly(A) repeats from 639-872, p28 from 1146-1814. length 2151 bases.
GRCH37 coord=1.277,473,298-277,473,968 = 675 bp.
NCBI map viewer position 13,320-14,347 = 1077 bp.
No sequences similar to U5, pol, env, u3 of HTLV.
There are no sequences similar to U5, pol, env, u3 of HTLV, and no viral particles are produced.
Do antibodies develop against HRES-1 proteins in humans?
Antibodies to HRES-1 induced p28 (from 1146=1814) occur in 52% of patients with SLE and 3.6% of healthy donors but not retrovirally infected patients.
The Gag protein of HRES-1 is controversial due to variable sequences. HRES-1 Gag capsid P15 antigen and the U1 sn-RNP complex.
THE ROLE OF HTLV-1 RELATED ENDOGENOUS RETROVIRAL SEQUENCE IN THE ETIOPATHOGENESIS OF SYSTEMIC LUPUS ERYTHEMATOSUS by Nancy S. Leo
What are LTR’s?
long terminal repeats (LTR) are identical sequences of DNA found at either end of retrotransposons formed by reverse transcription of retroviral RNA, used to insert their DNA into the host genome. They are about 640 base pairs with the 5' end serving as a promoter for the entire retroviral genome. The 3' end provides for nascent RNA polyadenylation. Inverted repeats (-3-25 BP) at the end of the LTR provide recognition sites for integrase.
How is the Baltimore classification of viruses constructed?
The Baltimore classification of viruses is based on how each one develops viral messenger RNA. Class I starts with dsDNA then mRNA herpes class II with ssDNA + strand, then dsDNA, parvovirus class III with dsRNA reovirus class IV with (+) ssRNA then ribosomes attach, picornavirus class V with (-) ssRNA mRNA copied by viral polymerase into (+) sense orthomyxovirus class VI with ssRNA-RT progressing to DNA/RNA then dsDNA, host integration then host RNA polymerase HIV class VII with dsDNA-RT, goes to covalently circular DNA(cccDNA), then mRNA which is transformed by RT to viral DNA hepatitis B.
what does Rab4 have to do with HRES-1?
The antisense strand of the HRES-1 encodes a 24-kD protein (p28 measured p25 calculated) HRES-1/Rab4. HRES-1/Rab4 is transcribed in the reverse direction from 1304 to 1068 = 236 bp, 8 exons, producing p24.
It is transactivated by the tat gene of HIV-1 and regulates the surface expression of CD4 through endosomal recycling.
The gene is expressed in PBL’s.
How variable is the HRES-1 gene?
There are 4 single-nucleotide polymorphisms in HRES1 (SNPs) within a 935-base pair interval. Alleles are associated with renal disease, and absence of lung disease while another is associated with the antiphospholipid syndrome in patients with SLE.
What is the difference between HTLV-1 and HTLV-2?
HTLV-1 is found in 20 primate species, shows evidence of multiple episodes of interspecies transmission, and is genetically diverse. HTLV-1 may cause myelopathy, uveitis, infectious dermatitis.
HTLV-2 found in only amerindian and african pigmy populations, spreading among iv drrg users. is associated with milder neurologic disorders and chronic pulmonary infection.
What is the genetic structure of infectious human endogenous retroviruses?
Human endogenous retroviruses (HERV) contain 2 LTRs, and between them gag, pol, and env sequences. Mutations frequently occur
What does the TNR sequence and retroviral genomes code for?
The TNR sequence in retroviral genomes code for micro-RNAs that regulate the apoptoses genes ERCC1 (excision-repair, complementing defective, in Chinese hamster, 1) and IER3 (radiation-inducible immediate-early gene).
What are some of the genes carried by structurally competent endogenous retroviruses?
U3 (Unique 3’) a sequence of 190-1200 nucleotides between PPT and R near the 3’end of viral RNA present once in viral genome RNA, twice in viral DNA as part of the LTR. It contains promoter-enhancer sequences that control viral RNA transcription from the 5’ LTR.
R (Repeat) a short 5-250 nucleotide sequence repeated at both ends of genomic RNA, and present twice in viral DNA as part of the LTR.
U5 (unique 5’) a sequence (70-250 nucleotides) position between R and the primer binding site.
PBS (primer-binding site) a region (18 nucleotides beginning 5”TGG) adjacent to U5 and complementary to the 3’ terminus of a specific host tRNA species. It is the binding site for a tRNA that functions as a primer for reverse transcriptase to initiate synthesis of the minus strand of viral DNA.
The second of four coding domains in replication-competent retroviruses is pro that encodes part of the poly protein (Gag-Pro or Gag-Pro-Pol) was created products always include protease (PR) and sometimes d UTPase.
The third of four coding domains is pol whose cleavage products always include reverse transcriptase and integrates and some lentiviruses dUTPase.
ENV is the last of four coding domains in a replication-competent retroviruses whose cleaved products and code SU (surface) and TM (transmembrane) structural proteins of the viral envelope.
Other genomic sites include SD (splice donor site), SA (splice acceptor site), RPE (rev or Rex response element), CTE (constitutive transport element), PPT (polypurine tract), poly (A) tract-usually added post transcriptionally.
Relative sizes are-
U3 R U5 genome (R to R)
HTLV-1 353 228 221 8.528
HIV-1 454 98 84 9,181
HIV-2 457 174 129 9,671
What are the genes and where they located HTLV-1?
In HTLV-1 the genes are situated as follows-
1) R (1-228) includes a RexRE element
2) U5 (229-405)
3) PBS (406-423) primer for minus strand DNA synthesis is tRNA Pro.
4) Gag (450-1737) Pr55 splits into MA, CA, and NC proteins.
5) Pro (1718-2402) a frameshift produces a gag pro polyprotein.
6) Pol (2245-4834) frameshift mutation and p95 cleavage produces the RT and IN domains.
env (4829-6293) produces SU and TM proteins.
7) Rex (4773-4832, 6951-7458) produced from a doubly spliced tax/Rex mRNA.
8) Tax (4829-4832, 6951-8006) from a doubly spliced tax/Rex mRNA.
9) PPT (7910-7926)
10) U3 (7927-8279) tax interacts with cellular factors at these sites in the 5’ LTR of the provirus to activate viral transcription.
11) R (8280-8507) the secondary structure provides the polyadenylation signal-a special case for HTLV.
What conventions govern the naming of proteins?
Proteins are designated by p, glycoproteins by gp, and glycosylated precursor proteins by gPr and phosphoproteins by pp, place before the approximate molecular weight e.g. p24, gp120. Precursor proteins use the prefix pr, or if not further processed by P. Onc gene names are three letters long, lowercase italics, and onc protein names are the same letters with the first letter capitalized.
What transcription factor binding sites are present on HRES-1?
HRES-1 has binding sites (on nucleotides) for IRF-1 (647-667), IRF-4 (922-942), IRF-7 (1017-1037), IRF-3 (1003-1123), ISRE (1110-1130), GATA-3 (714-726, 1002-1014), Ikaros proteins (262-274, 904-916, 920-932, 925-937), STAT (555-973), Nfat (1116-1134), and NRSE (neural restrictive silencing factor 1247-1267).
